Benzoheterocyclic derivatives

ABSTRACT

A benzoheterocyclic derivative of the following formula [1]:  
                 
 
     and pharmaceutically acceptable salts thereof, which show excellent anti-vasopressin activity, vasopressin agonistic activity and oxytocin antagonistic activity, and are useful as a vasopressin antagonist, vasopressin agonist or oxytocin antagonist.

TECHNICAL FIELD

[0001] The present invention relates to novel benzoheterocyclic derivatives having excellent vasopressin antagonistic activities, vasopressin agonistic activities and oxytocin antagonistic activities.

BACKGROUND ART

[0002] Various benzoheterocyclic compounds analogous to the compounds of the present invention have been known to have anti-vasopressin activities in European Patent Publication No. 0382128 (published on Aug. 15, 1990), WO 91/05549 (published on May 2, 1991), WO 91/16916 (published on Nov. 14, 1991), WO 94/08582 (published on Apr. 28, 15, 1994), WO 94/12476 (published on Jun. 9, 1994), JP-A-5-320135 (published on Dec. 3, 1993), JP-A-6-16643 (published on Jan. 25, 1994), and JP-A-6-157480 (published on Jun. 3, 1994), among which, for example, JP-A-6-16643 discloses the following compounds.

[0003] Some other literatures disclose various benzoheterocyclic compounds which are analogous to the compounds of the present invention in the chemical structure but are different in the pharmacological properties. For example, EP-A-294647 discloses some analogous compounds having positive inotropic action, vasodilating activity and platelet agglutination inhibiting activity, wherein the intermediate compounds of the following formula are also disclosed.

[0004] U.S. Pat. Nos. 3,542,760 (issued Nov. 24, 1970), 3,516,987 (issued Jun. 23, 1970) and 3,458,498 (issued Jul. 29, 1969) disclose also the following compounds which are useful as diuretics, hypoglycemics, antibacterials or anti-convulsants.

[0005] J. Chem. Soc. Perkin Trans., 1, 1985, pp. 1381-1385 discloses the following compounds but does not mention any pharmacological activity thereof.

[0006] Disclosure of Invention

[0007] An object of the present invention is to provide a benzoheterocyclic derivative of the following formula [1]:

[0008] wherein G is a group of the formula:

[0009] or a group of the formula:

[0010] R¹ is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group, an amino group having optionally a lower alkyl substituent, a carboxy-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, or an aminocarbonyl-lower alkoxy group having optionally a lower alkyl substituent,

[0011] R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different, and each a hydrogen atom, a lower alkyl group having optionally a hydroxy substituent or a benzoyl group having optionally a halogen substituent on the phenyl ring); a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group; a lower alkanoyl group; or a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which m and u are each 0 or 1, but both m and n should not be simultaneously 0, A is a lower alkylene group, R⁶ and R⁷ are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group),

[0012] R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group,

[0013] or R² and R³ may bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group,

[0014] R is a pyridylcarbonyl group which may optionally have a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group; a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; a cycloalkylcarbonyl group; or a group of the formula:

[0015]  (in which p is 1 or 2, R⁸ is a hydrogen atom, a lower alkyl group, a hydroxy group, an amino group having optionally a lower alkanoyl substituent, a nitro group, a halogen atom or a lower alkoxy group, R⁹ is a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ is a hydrogen atom, a lower alkyl group, or a lower alkanoyl group having optionally a halogen substituent, R¹¹ is a lower alkyl group, a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the lower alkanoyl moiety, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a lower alkoxycarbonyl group having optionally a halogen substituent, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a phenoxy-lower alkoxycarbonyl group, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a phenyl-lower alkoxycarbonyl group, a group of the formula:

[0016]  a tetrahydroisoquinolylcarbonyl group, a benzoyl-lower alkyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a lower alkylsulfonyl group, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a phenyl-lower alkenylcarbonyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, or R¹⁰ and R¹¹ may bind together with the nitrogen atom to which they bond to form an isoindoline ring); a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a cycloalkyl group; a lower alkyl group; a lower alkylthio group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a saturated or unsaturated 5- to 11-membered heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: 13 (A)_(m)—CHR¹²R¹³ (in which A is the same as defined above, R¹² is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R¹³ is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1)),

[0017] X is a methylene group, a single bond, a group of the formula: ═CH— or a group of the formula: —NR¹⁴— (in which R¹⁴ is a hydrogen atom, a lower alkyl group or a lower alkanoyl group),

[0018] Y is a group of the formula: —NR^(A) (in which R^(A) is a hydrogen atom, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: —ACONR^(B)R^(C) (in which R^(B) and R^(C) are the same or different and each a hydrogen atom or a lower alkyl group, or R^(B) and R^(C) may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group)),

[0019] provided that when R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different and each a hydrogen atom, a lower alkyl group or a benzoyl group), a hydrogen atom, a hydroxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group, a lower alkoxy group, a lower alkanoyloxy-substituted lower alkyl group, a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (m and u are the same as defined above, R⁶ and R⁷ are the same or different and each a hydrogen atom or a lower alkyl group, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group), or an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; or R² and R³ may bind together to form an oxo group or a lower alkylidene group; and when R is a group of the formula:

[0020]  and R⁸ in said group is a hydrogen atom, a lower alkyl group, a hydroxy group, a halogen atom, a lower alkoxy group or an amino group, then R⁹ should not be a hydrogen atom, a phenyl-lower alkoxycarbonyl group, nor a group of the formula: —NR¹⁰R¹¹ (R¹¹ is a lower alkanoyl group or a phenoxy-lower alkanoyl group having optionally 1 to 3 substituents selected from a lower alkyl group and a lower alkoxy group on the phenyl ring), or

[0021] when R¹ is a hydrogen atom, R² is a hydrogen atom, an amino group, a mono-lower alkylamino group or a di-lower alkylamino group, or R² and R³ may bind together to form an oxo group, then R⁹ should not be a phenyl group having optionally a substituent selected from a hydroxy group, a lower alkyl group, a lower alkoxy group and a lower alkanoyloxy group on the phenyl ring, or

[0022] when R⁹ is a group of the formula:

[0023]  (n is 1 or 2), and G is a group of the formula:

[0024]  (R² and R³ are the same as defined above), then X should not be a methylene group nor a group of the formula: ═CH—, or

[0025] when one of R¹⁰ and R¹¹ is a hydrogen atom, the other should not be a lower alkyl group,

[0026] or a pharmaceutically acceptable salt thereof.

[0027] The present inventors have intensively studied and have found that the compounds of the formula [1] and a pharmaceutically acceptable salt thereof have excellent vasopressin antagonistic activities, vasopressin agonistic activities and excellent oxytocin antagonistic activities.

[0028] The compounds of the formula [1] of the present invention and a pharmaceutically acceptable salt thereof show excellent vasopressin antagonistic activity, for example, vasodilating activity, hypotensive activity, activity for inhibiting saccharide release in liver, activity for inhibiting growth of mesangium cells, water diuretic activity, platelet agglutination inhibitory activity, inhibitory activity for vomiting, activity for promoting urea excretion, inhibitory activity on secretion of factor VIII, activity for promoting heart function, activity for inhibiting constriction of mesangium cells, inhibitory activity on production of saccharide in liver, inhibitory activity on aldosterone secretion, inhibitory activity on production of endotheline, regulation activity on renin secretion, memory regulation activity, thermoregulation activity, activity for regulating production of prostaglandin, and hence, they are useful as vasodilators, hypotensive agents, water diuretics, platelet agglutination inhibitors, promoters for urea excretion, agent for heart failure, agent for renal failure, etc., and are used in the prophylaxis or treatment of hypertension, edema, ascites, heart failure, renal function disorder, vasopressin parasecretion syndrome (SIADH), hepatocirrhosis, hyponatremia, hypokalemia, diabetes, circulation disorder, motion sickness, water metabolism disorder, renal failure, various diseases associated with ischemic, and the like. Besides, the compounds of the present invention and a pharmaceutically acceptable salt thereof are characteristic in very few side effects and a prolonged action for a long time in a living body.

[0029] The compounds [1] of the present invention and a pharmaceutically acceptable salt thereof also show vasopressin agonistic activities, for example, effects on various urinary disorders, polyuria or hemostatic disorders, and hence, they are useful in the prophylaxis or treatment of pollakisuria, diabetes insipidus, urine incontinence, enuresis, especially nocturnal enuresis, spontaneous hemorrhage, hemophilia, von Willebrand's disease, uremia, congenital and acquired platelet dysfunction, hemostatic derangement caused by surgical procedures or accidental trauma, or hepatic cirrhosis.

[0030] In addition, the compounds [1] of the present invention and a pharmaceutically acceptable salt thereof also show oxytocin antagonistic activities, for example, inhibitory effect on uterine smooth muscle constriction, inhibitory effect on milk secretion, inhibitory effect on synthesis and secretion of prostaglandin, and vasodilating activity, and hence, they are useful in the protection or treatment of oxytocin-associated diseases, especially premature delivery, dysmenorrhea, endometritis, or in stopping labor preparatory to Caesarian delivery.

[0031] The benzoheterocyclic derivatives of the formula [1] of the present invention especially include the following compounds.

[0032] (1) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a methylene group, R¹ is the same as defined above in the definition for the formula [1], R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same as defined above in the definition for the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent on the phenyl ring and a pyridyl group on the pyridine ring.

[0033] (2) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (1), and R² is a hydrogen atom.

[0034] (3) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (1), and R² is a hydroxy group.

[0035] (4) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (1), and R² is a carboxy-substituted lower alkyl group.

[0036] (5) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (1), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0037] (6) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (1), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0038] (7) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (1), and R² is a lower alkanoyl group.

[0039] (8) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (1), and R² and R³ bind together to form an oxo group.

[0040] (9) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (1), and R² and R³ bind together to form a lower alkylidene group.

[0041] (10) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (1), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0042] (11) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (1), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0043] (12) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (1), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0044] (13) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a methylene group, R¹ is the same as defined above in the definition for the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the definition for the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0045]  (R⁹ and p are the same as defined above, and R⁸ is a hydrogen atom).

[0046] (14) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (13), and R² is a hydrogen atom.

[0047] (15) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (13), and R² is a hydroxy group.

[0048] (16) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (13), and R² is a carboxy-substituted lower alkyl group.

[0049] (17) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (13), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0050] (18) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (13), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0051] (19) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (13), and R² is a lower alkanoyl group.

[0052] (20) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (13), and R² and R³ bind together to form an oxo group.

[0053] (21) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (13), and R² and R³ bind together to form a lower alkylidene group.

[0054] (22) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (13), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0055] (23) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (13), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0056] (24) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (13), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0057] (25) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a methylene group, R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0058]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a lower alkyl group).

[0059] (26) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (25), and R² is a hydrogen atom.

[0060] (27) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (25), and R² is a hydroxy group.

[0061] (28) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (25), and R² is a carboxy-substituted lower alkyl group.

[0062] (29) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (25), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0063] (30) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (25), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0064] (31) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (25), and R² is a lower alkanoyl group.

[0065] (32) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (25), and R² and R³ bind together to form an oxo group.

[0066] (33) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (25), and R² and R³ bind together to form a lower alkylidene group.

[0067] (34) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (25), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0068] (35) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (25), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0069] (36) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (25), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0070] (37) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a methylene group, R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0071]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a hydroxy group).

[0072] (38) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (37), and R² is a hydrogen atom.

[0073] (39) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (37), and R² is a hydroxy group.

[0074] (40) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (37), and R² is a carboxy-substituted lower alkyl group.

[0075] (41) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (37), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0076] (42) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (37), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0077] (43) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (37), and R² is a lower alkanoyl group.

[0078] (44) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (37), and R² and R³ bind together to form an oxo group.

[0079] (45) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (37), and R² and R³ bind together to form a lower alkylidene group.

[0080] (46) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (37), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0081] (47) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (37), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0082] (48) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (37), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0083] (49) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is methylene group, R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0084]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a nitro group).

[0085] (50) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (49), and R² is a hydrogen atom.

[0086] (51) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (49), and R² is a hydroxy group.

[0087] (52) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (49), and R² is a carboxy-substituted lower alkyl group.

[0088] (53) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (49), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0089] (54) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (49), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0090] (55) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (49), and R² is a lower alkanoyl group.

[0091] (56) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (49), and R² and R³ bind together to form an oxo group.

[0092] (57) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (49), and R² and R³ bind together to form a lower alkylidene group.

[0093] (58) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (49), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0094] (59) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (49), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0095] (60) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (49), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0096] (61) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a methylene group, R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0097]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a halogen atom).

[0098] (62) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (61), and R² is a hydrogen atom.

[0099] (63) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (61), and R² is a hydroxy group.

[0100] (64) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (61), and R² is a carboxy-substituted lower alkyl group.

[0101] (65) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (61), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0102] (66) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (61), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0103] (67) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (61), and R² is a lower alkanoyl group.

[0104] (68) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (61), and R² and R³ bind together to form an oxo group.

[0105] (69) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (61), and R² and R³ bind together to form a lower alkylidene group.

[0106] (70) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (61), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0107] (71) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (61), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0108] (72) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (61), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0109] (73) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a methylene group, R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0110]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a lower alkoxy group).

[0111] (74) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (73), and R² is a hydrogen atom.

[0112] (75) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (73), and R² is a hydroxy group.

[0113] (76) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (73), and R² is a carboxy-substituted lower alkyl group.

[0114] (77) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (73), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0115] (78) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (73), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0116] (79) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (73), and R² is a lower alkanoyl group.

[0117] (80) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (73), and R² and R³ bind together to form an oxo group.

[0118] (81) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (73), and R² and R³ bind together to form a lower alkylidene group.

[0119] (82) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (73), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0120] (83) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (73), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0121] (84) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (73), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group

[0122] (85) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a group of the formula: —NR¹⁴— (R¹⁴ is the same as defined above in the formula [1]), R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent on the phenyl ring and a pyridyl group on the pyridine ring.

[0123] (86) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (85), and R² is a hydrogen atom.

[0124] (87) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (85), and R² is a hydroxy group.

[0125] (88) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (85), and R² is a carboxy-substituted lower alkyl group.

[0126] (89) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (85), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0127] (90) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (85), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0128] (91) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (85), and R² is a lower alkanoyl group.

[0129] (92) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (85), and R² and R³ bind together to form an oxo group.

[0130] (93) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (85), and R² and R³ bind together to form a lower alkylidene group.

[0131] (94) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (85), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0132] (95) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (85), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0133] (96) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (85), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0134] (97) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a group of the formula: —NR¹⁴— (R¹⁴ is the same as defined above in the formula [1]), R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0135]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a hydrogen atom).

[0136] (98) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (97), and R² is a hydrogen atom.

[0137] (99) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (97), and R² is a hydroxy group.

[0138] (100) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (97), and R² is a carboxy-substituted lower alkyl group.

[0139] (101) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (97), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0140] (102) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (97), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0141] (103) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (97), and R² is a lower alkanoyl group.

[0142] (104) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (97), and R² and R³ bind together to form an oxo group.

[0143] (105) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (97), and R² and R³ bind together to form a lower alkylidene group.

[0144] (106) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (97), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0145] (107) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (97), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0146] (108) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (97), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0147] (109) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a group of the formula: —NR¹⁴— (R¹⁴ is the same as defined above in the formula [1]), R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0148]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a lower alkyl group).

[0149] (110) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (109), and R² is a hydrogen atom.

[0150] (111) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (109), and R² is a hydroxy group.

[0151] (112) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (109), and R² is a carboxy-substituted lower alkyl group.

[0152] (113) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (109), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0153] (114) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (109), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0154] (115) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (109), and R² is a lower alkanoyl group.

[0155] (116) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (109), and R² and R³ bind together to form an oxo group.

[0156] (117) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (109), and R² and R³ bind together to form a lower alkylidene group.

[0157] (118) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (109), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0158] (119) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (109), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0159] (120) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (109), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0160] (121) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a group of the formula: —NR¹⁴— (R¹⁴ is the same as defined above in the formula [1]), R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0161]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a hydroxy group).

[0162] (122) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (121), and R² is a hydrogen atom.

[0163] (123) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (121), and R² is a hydroxy group.

[0164] (124) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (121), and R² is a carboxy-substituted lower alkyl group.

[0165] (125) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (121), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0166] (126) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (121), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0167] (127) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (121), and R² is a lower alkanoyl group.

[0168] (128) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (121), and R² and R³ bind together to form an oxo group.

[0169] (129) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (121), and R² and R³ bind together to form a lower alkylidene group.

[0170] (130) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (121), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0171] (131) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (121), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0172] (132) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (121), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0173] (133) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a group of the formula: —NR¹⁴— (R¹⁴ is the same as defined above in the formula [1]), R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0174]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a nitro group).

[0175] (134) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (133), and R² is a hydrogen atom.

[0176] (135) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (133), and R² is a hydroxy group.

[0177] (136) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (133), and R² is a carboxy-substituted lower alkyl group.

[0178] (137) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (133), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0179] (138) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (133), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0180] (139) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (133), and R² is a lower alkanoyl group.

[0181] (140) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (133), and R² and R³ bind together to form an oxo group.

[0182] (141) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (133), and R² and R³ bind together to form a lower alkylidene group.

[0183] (142) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (133), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0184] (143) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (133), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0185] (144) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (133), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0186] (145) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a group of the formula: —NR¹⁴— (R¹⁴ is the same as defined above in the formula [1]), R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0187]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a halogen atom).

[0188] (146) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (145), and R² is a hydrogen atom.

[0189] (147) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (145), and R² is a hydroxy group.

[0190] (148) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (145), and R² is a carboxy-substituted lower alkyl group.

[0191] (149) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (145), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0192] (150) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (145), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0193] (151) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (145), and R² is a lower alkanoyl group.

[0194] (152) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (145), and R² and R³ bind together to form an oxo group.

[0195] (153) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (145), and R² and R³ bind together to form a lower alkylidene group.

[0196] (154) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (145), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0197] (155) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (145), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0198] (156) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (145), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0199] (157) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a group of the formula: —NR¹⁴— (R¹⁴ is the same as defined above in the formula [1]), R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0200]  (R⁹ and p are the same as defined above in the formula [1], and R⁸ is a lower alkoxy group).

[0201] (158) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (157), and R² is a hydrogen atom.

[0202] (159) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (157), and R² is a hydroxy group.

[0203] (160) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (157), and R² is a carboxy-substituted lower alkyl group.

[0204] (161) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (157), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0205] (162) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (157), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0206] (163) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (157), and R² is a lower alkanoyl group.

[0207] (164) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (157), and R² and R³ bind together to form an oxo group.

[0208] (165) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (157), and R² and R³ bind together to form a lower alkylidene group.

[0209] (166) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (157), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0210] (167) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (157), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0211] (168) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (157), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0212] (169) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a methylene group, R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a 9-oxofluorenyl group.

[0213] (170) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (169), and R² is a hydrogen atom.

[0214] (171) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (169), and R² is a hydroxy group.

[0215] (172) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (169), and R² is a carboxy-substituted lower alkyl group.

[0216] (173) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (169), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0217] (174) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (169), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0218] (175) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (169), and R² is a lower alkanoyl group.

[0219] (176) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (169), and R² and R³ bind together to form an oxo group.

[0220] (177) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (169), and R² and R³ bind together to form a lower alkylidene group.

[0221] (178) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (169), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0222] (179) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (169), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0223] (180) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (169), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group.

[0224] (181) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R²)(R³)—X—, X is a group of the formula: —NR¹⁴— (R¹⁴ is the same as defined above in the formula [1]), R¹ is the same as defined above in the formula [1], R² is a group of the formula: —NR⁴R⁵ (R⁴ and R⁵ are the same as defined above in the formula [1]), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a 9-oxofluorenyl group.

[0225] (182) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (181), and R² is a hydrogen atom.

[0226] (183) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (181), and R² is a hydroxy group.

[0227] (184) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (181), and R² is a carboxy-substituted lower alkyl group.

[0228] (185) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (181), and R² is a lower alkoxycarbonyl-substituted lower alkyl group.

[0229] (186) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (181), and R² is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0230] (187) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹, R³ and R are the same as defined in above (181), and R² is a lower alkanoyl group.

[0231] (188) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (181), and R² and R³ bind together to form an oxo group.

[0232] (189) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (181), and R² and R³ bind together to form a lower alkylidene group.

[0233] (190) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (181), and R² and R³ bind together to form a lower alkoxy-substituted lower alkylidene group.

[0234] (191) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (181), and R² and R³ bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0235] (192) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R¹ and R are the same as defined in above (181), and R² and R³ bind together to form a phenyl-substituted lower alkylidene group

[0236] Each group in the above formula [1] specifically means the following groups.

[0237] The lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.

[0238] The lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, etc.

[0239] The halogen atom is fluorine atom, chlorine atom, bromine atom or iodine atom.

[0240] The lower alkanoyloxy group includes a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert-butyl-carbonyloxy, hexanoyloxy, and the like.

[0241] The lower alkanoyl group having optionally a halogen substituent includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms which may optionally be substituted by 1 to 3 halogen atoms, for example, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichloropropionoyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6-bromohexanoyl, 5,6-dibromohexanoyl, and the like.

[0242] The amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group being optionally substituted by 1 to 2 groups selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, acetylaminomethoxy, 1-acetylaminoethoxy, 2-propionylaminoethoxy, 3-isopropionylaminopropoxy, 4-butyrylaminobutoxy, 5-pentanoylaminopentyloxy, 6-hexanoylaminohexyloxy, formylaminomethoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminoproxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, (N-ethyl-N-propylamino)methoxy, 2-(N-methyl-N-hexylamino)ethoxy, and the like.

[0243] The amino group having optionally a lower alkyl substituent includes an amino group which may optionally be substituted by 1 to 2 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, and the like.

[0244] The lower alkoxycarbonyl-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonylmethoxy, 3-methoxycarbonylpropoxy, ethoxycarbonylmethoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, hexyloxycarbonylmethoxy, and the like.

[0245] The carboxy-substituted lower alkoxy group includes a carboxyalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, 1,1-dimethyl-2-carboxyethoxy, 2-methyl-3-carboxypropoxy, and the like.

[0246] The aminocarbonyl-lower alkoxy group having a lower alkyl substituent includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an aminocarbonyl group having 1 to 2 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, methylaminocarbonylmethoxy, 1-ethylaminocarbonylethoxy, 2-propylaminocarbonylethoxy, 3-isopropylaminocarbonylpropoxy, 4-butylaminocarbonylbutoxy, 5-pentylaminocarbonylpentyloxy, 6-hexylaminocarbonylhexyloxy, dimethylaminocarbonylmethoxy, 3-diethylaminocarbonylpropoxy, diethylaminocarbonylmethoxy, (N-ethyl-N-propylamino)carbonylmethoxy, 2-(N-methyl-N-hexylamino)carbonylethoxy, and the like.

[0247] The benzoyl group having optionally a halogen substituent on the phenyl ring includes a benzoyl group having optionally 1 to 3 halogen substituents on the phenyl ring, for example, benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-fluorobenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 3-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 4-iodobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 3,4-difluorobenzoyl, 3,5-dibromobenzoyl, 3,4,5-trichlorobenzoyl, and the like.

[0248] The carboxy-substituted lower alkyl group includes a carboxylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxyethyl, 2-methyl-3-carboxylpropyl, and the like.

[0249] The lower alkoxycarbonyl-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonylmethyl, 3-methoxycarbonypropyl, ethoxycarbonylmethyl, 3-ethoxycarbonylpropyl, 4-ethoxycarbonylbutyl, 5-isopropoxycarbonylpentyl, 6-propoxycarbonylhexyl, 1,1-dimethyl-2-butoxycarbonylethyl, 2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, hexyloxycarbonylmethyl, and the like.

[0250] The amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent includes a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, 2-aminoacetyloxy, 3-aminopropionyloxy, 2-aminopropionyloxy, 4-aminobutyryloxy, 2,2-dimethyl-3-aminopropionyloxy, 5-aminopentanoyloxy, 6-aminohexanoyloxy, 2-methyl-3-aminopropionyloxy, 2-methylaminoacetyloxy, 3-ethylaminopropionyloxyl, 2-propylaminopropionyloxy, 4-isopropylaminobutyryloxy, 4-butylaminobutyryloxy, 4-tert-butyaminobutyryloxy, 5-pentylaminopentanoyloxy, 6-hexylaminohexanoyloxyl, 2-dimethylaminoacetyloxy, 3-diethylaminopropionyloxy, 2-dimethylaminopropionyloxy, 2-(N-ethyl-N-propylamino)acetyloxy, 3-(N-methyl-N-hexylamino)propionyloxy, and the like.

[0251] The lower alkanoyl group includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, t-butylcarbonyl, hexanoyl, and the like.

[0252] The lower alkylidene group includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms, for example, methylidene, ethylidene, propylidene, isopropylidene, butylidene, pentylidene, hexylidene, and the like.

[0253] The lower alkoxycarbonyl-substituted lower alkylidene group includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, ethoxycarbonylmethylidene, 2-methoxycarbonylethylidene, 3-isopropoxycarbonylpropylidene, 2-propoxycarbonylisopropylidene, 4-butoxycarbonylbutylidene, 5-pentyloxycarbonylpentylidene, 6-hexyloxycarbonylhexylidene, and the like.

[0254] The lower alkoxy-substituted lower alkylidene group includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxymethylidene, 2-ethoxyethylidene, 3-propoxypropylidene, 2-isopropoxyisopropylidene, 4-butoxybutylidene, 5-pentyloxypentylidene, 6-hexyloxyhexylidene, and the like.

[0255] The phenyl-substituted lower alkylidene group includes a straight chain or branched chain alkylidene having 1 to 6 carbon atoms which is substituted by a phenyl group, for example, phenylmethylidene, 2-phenylethylidene, 3-phenylpropylidene, 2-phenylpropylidene, 4-phenylbutylidene, 5-phenylpentylidene, 6-phenylhexylidene, and the like.

[0256] The lower alkylene group includes a straight chain or branched chain alkylene group having 1 to 6 carbon atoms, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, hexamethylene, etc.

[0257] The amino-substituted lower alkyl group having optionally a lower alkyl substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diethylaminoethyl, 2-dimethylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, and the like.

[0258] The 5- to 7-membered saturated heterocyclic group which is formed by binding R⁶ and R⁷ or R^(B) and R^(C) together with the adjacent nitrogen atom to which they bond with or without being intervening with another nitrogen atom or an oxygen atom, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, homopiperazinyl, and the like.

[0259] The above heterocyclic group having a substituent selected from a lower alkyl group and a phenyl-lower alkyl group includes the above mentioned heterocyclic groups having 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by 1 to 2 phenyl groups, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 1-methylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-ethylhomopiperazinyl, 4-methylhomopiperazinyl, 4-hexylpiperazinyl, 4-diphenylmethylpiperazinyl, 4-benzylpiperazinyl, 3-methyl-4-benzylpiperazinyl, 3-(2-phenylethyl)pyrrolidinyl, 2-(1-phenylethyl)pyrrolidinyl, 4-(3-phenylpropyl)piperidinyl, 3-(4-phenylbutyl)morpholino, 3-(5-phenylpentyl)piperidinyl, 4-(6-phenylhexyl)piperazinyl, and the like.

[0260] The above heterocyclic group substituted by a lower alkyl group includes the above mentioned heterocyclic groups being substituted by 1 to 3 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 1-methylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-methylhomopiperazinyl, 4-hexylpiperazinyl, and the like.

[0261] The phenyl group having optionally a lower alkyl substituent includes a phenyl group which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-propylphenyl, 4-butylphenyl, 2-pentylphenyl, 3-hexylphenyl, 3,4-dimethylphenyl, 3,4,5-trimethylphenyl, and the like.

[0262] The phenyl group having optionally a lower alkoxy substituent includes a phenyl group which may optionally have 1 to 3 straight chain or branched chain alkoxy substituents having 1 to 6 carbon atoms, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-propoxyphenyl, 4-butoxyphenyl, 2-pentyloxyphenyl, 3-hexyloxyphenyl, 2,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 3,4,5-trimethoxyphenyl, and the like.

[0263] The pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring includes a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms and a pyridyl group on the pyridine ring, for example, pyridylcarbonyl, 2-phenylpyridylcarbonyl, 3-phenylpyridylcarbonyl, 4-phenylpyridylcarbonyl, 2-(2-methylphenyl)pyridylcarbonyl, 3-(2-ethylphenyl)pyridylcarbonyl, 4-(3-propylphenyl)pyridylcarbonyl, 2-(4-butylphenyl)pyridylcarbonyl, 3-(2-pentylphenyl)pyridylcarbonyl, 4-(3-hexylphenyl)pyridylcarbonyl, 2-(3,4-dimethylphenyl)pyridylcarbonyl, 3-(3,4,5-trimethylphenyl)pyridylcarbonyl, 3-(2-pyridyl)pyridylcarbonyl, 2-(3-pyridyl)pyridylcarbonyl, 4-(4-pyridyl)pyridylcarbonyl, and the like.

[0264] The phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and said alkyl moiety having optionally a hydroxy substituent, and the phenyl ring may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a halogen atom, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, 2-chlorobenzyl, 2-(3-chlorophenyl)ethyl, 2-fluorobenzyl, 1-(4-chlorophenyl)ethyl, 3-(2-fluorophenyl)propyl, 4-(3-fluorophenyl)butyl, 5-(4-fluorophenyl)pentyl, 1,1-dimethyl-2-(2-bromophenyl)ethyl, 6-(3-bromophenyl)hexyl, 4-bromobenzyl, 2-(2-iodophenyl)ethyl, 1-(3-iodophenyl)ethyl, 3-(4-iodophenyl)propyl, 3,4-dichlorobenzyl, 3,5-dichlorobenzyl, 2,6-dichlorobenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 3,4-difluorobenzyl, 3,5-dibromobenzyl, 3,4,5-trichlorobenzyl, 3,5-dichloro-4-hydroxybenzyl, 3,5-dimethyl-4-hydroxybenzyl, 2-methoxy-3-chlorobenzyl, 2-methylbenzyl, 2-(2-methylphenyl)ethyl, 1-(3-methylphenyl)ethyl, 3-(4-methylphenyl)propyl, 4-(2-ethylphenyl)butyl, 5-(3-propylphenyl)pentyl, 6-(4-butylphenyl)hexyl, 2-(2-pentylphenyl)ethyl, 1-(3-hexylphenyl)ethyl, 3-(3,4-dimethylphenyl)propyl, 2-(3,4,5-trimethylphenyl)ethyl, (2-methyl-6-chlorophenyl)methyl, 3-phenyl-2-hydroxypropyl, 2-phenyl-2-hydroxyethyl, 1-phenyl-1-hydroxymethyl, 3-(4-methylphenyl)-3-hydroxypropyl, 4-(3-chlorophenyl)-4-hydroxybutyl, 5-(2-bromophenyl)-5-hydroxypentyl, 6-(4-fluorophenyl)-6-hydroxyhexyl, and the like.

[0265] The phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a phenoxy group having optionally 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, phenoxymethyl, 2-phenoxyethyl, 1-phenoxyethyl, 4-phenoxybutyl, 5-phenoxypentyl, 6-phenoxyhexyl, 1,1-dimethyl-2-phenoxyethyl, 2-methyl-3-phenoxypropyl, (2-methylphenoxy)methyl, 2-(2-methylphenoxy)ethyl, 3-phenoxypropyl, 4-(3-methylphenoxy)butyl, 5-(2-ethylphenoxy)pentyl, 6-(3-propylphenoxy)hexyl, 4-(butylphenoxy)methyl, 2-(2-pentylphenoxy)ethyl, 1-(3-hexylphenoxy)ethyl, 3-(3,4-dimethylphenoxy)propyl, 2-(3,4,5-trimethylphenoxy)ethyl, and the like.

[0266] The phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the alkanoyl moiety includes a phenoxyalkanoyl group which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenyl group, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms being substituted by 1 to 3 halogen atoms, an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, a nitro group, an amino group substituted by a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a halogen atom on the phenyl ring, and the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which may optionally have 1 to 3 halogen substituents, for example, 2-phenoxyacetyl, 2-phenoxypropionyl, 3-phenoxypropionyl, 2-phenoxybutyryl, 4-phenoxybutyryl, 2,2-dimethyl-3-phenoxypropionyl, 5-phenoxypentanoyl, 6-phenoxyhexanoyl, 2-(2-chlorophenoxy)acetyl, 2-(3-chlorophenoxy)acetyl, 2-(4-chlorophenoxy)acetyl, 2-(2-fluorophenoxy)acetyl, 2-(3-fluorophenoxy)acetyl, 3-(4-fluorophenoxy)propionyl, 2-(2-bromophenoxy)propionyl, 4-(3-bromophenoxy)butyryl, 5-(4-bromophenoxy)pentanoyl, 6-(2-iodophenoxy)hexanoyl, 2-(3-iodophenoxy)acetyl, 3-(4-iodophenoxy)propionyl, 4-(3,4-dichlorophenoxy)butyryl, 2-(3,4-dichlorophenoxy)acetyl, 2-(2,6-dichlorophenoxy)acetyl, 2-(2,3-dichlorophenoxy)acetyl, 2-(2,4-dichlorophenoxy)acetyl, 2-(3,4-difluorophenoxy)acetyl, 3-(3,5-dibromophenoxy)propionoyl, 2-(3,4,5-trichlorophenoxy)acetyl, 2-(2-methylphenoxy)acetyl, 2-(3-methylphenoxy)acetyl, 2-(4-methylphenoxy)acetyl, 3-(2-ethylphenoxy)propionyl, 2-(3-ethylphenoxy)propionyl, 4-(4-ethylphenoxy)butyryl, 5-(4-isopropylphenoxy)pentanoyl, 6-(3-butylphenoxy)hexanoyl, 3-(4-pentylphenoxy)propionyl, 2-(4-hexylphenoxy)acetyl, 2-(3,4-dimethylphenoxy)acetyl, 2-(3,4-diethylphenoxy)acetyl, 2-(2,4-dimethylphenoxy)acetyl, 2-(2,5-dimethylphenoxy)acetyl, 2-(2,6-dimethylphenoxy)acetyl, 2-(3,4,5-trimethylphenoxy)acetyl, 2-(3-chloro-4-methylphenoxy)acetyl, 2-(3-dimethylaminophenoxy)acetyl, 2-(3-nitrophenoxy)acetyl, 2-(2-methoxyphenoxy)acetyl, 2-(3-methoxyphenoxy)acetyl, 2-(4-methoxyphenoxy)acetyl, 2-(2-phenylphenoxy)acetyl, 2-(2-trifluoromethylphenoxy)acetyl, 3-(2-aminophenoxy)propionyl, 4-(4-ethylaminophenoxy)butyryl, 5-(2,3-dimethoxyphenoxy)pentanoyl, 6-(2,4,6-trimethoxyphenoxy)hexanoyl, 3-(2-ethoxyphenoxy)propionyl, 4-(3-propoxyphenoxy)propionyl, 2-(4-butoxyphenoxy)acetyl, 3-(4-pentyloxyphenoxy)propionyl, 4-(4-hexyloxyphenoxy)butyryl, 3-(2-nitrophenoxy)propionyl, 4-(4-nitrophenoxy)butyryl, 3-(3-phenylphenoxy)propionyl, 4-(4-phenylphenoxy)butyryl, 5-[3-(2,2,2-trichloroethyl)phenoxy]pentanoyl, 6-[4-(5-bromohexyl)phenoxy]hexanoyl, 2-(4-phenyl-2-methoxyphenoxy)acetyl, 2-(2-phenyl-4-methylphenoxy)acetyl, 2-(2,4,6-trinitrophenoxy)acetyl, 2-(2,4-dinitrophenoxy)acetyl, 2-(3-phenyl-2-dimethylaminophenoxy)acetyl, 2-phenoxy-2,2-difluoroacetyl, 3-(3-dimethylaminophenoxy)-3-bromopropionyl, 4-(3-nitrophenoxy)-3,4,4-trichlorobutyryl, 5-(2-methoxyphenoxy)-5-iodopentanoyl, 2-(2,6-dichlorophenoxy)-2-chloroacetyl, 2-(4-methyl phenoxy)-2,2,-difluoroacetyl, 2-(2-phenylphenoxy)-2,2-difluoroacetyl, 6-(2-phenylphenoxy)-6-bromohexanoyl, 2-(2-acetylaminophenoxy)acetyl, and the like.

[0267] The aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group includes an aminocarbonyl group which may optionally have 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a pyridyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl, pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, N-ethyl-N-(pyridylmethyl)aminocarbonyl, N-ethyl-N-benzylaminocarbonyl, benzylaminocarbonyl, (2-phenylethyl)aminocarbonyl, (1-phenylethyl)aminocarbonyl, (3-phenylpropyl)aminocarbonyl, (4-phenybutyl)aminocarbonyl, (5-phenylpentyl)aminocarbonyl, (6-phenylhexyl)aminocarbonyl, N-methyl-N-benzylaminocarbonyl, pyridylmethylaminocarbonyl, (2-pyridylethyl)aminocarbonyl, (3-pyridylpropyl)aminocarbonyl, (4-pyridylbutyl)aminocarbonyl, (5-pyridylpentyl)aminocarbonyl, (6-pyridylhexyl)aminocarbonyl, N-(pyridylmethyl)-N-benzylaminocarbonyl, N-methyl-N-(pyridylmethyl)aminocarbonyl, and the like.

[0268] The benzoyl group having optionally a lower alkyl substituent on the phenyl ring includes a benzoyl group having optionally 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, benzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-ethylbenzoyl, 3-propylbenzoyl, 4-butylbenzoyl, 2-pentylbenzoyl, 3-hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, and the like.

[0269] The cycloalkyl group includes a cycloalkyl group having 3 to 8 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like.

[0270] The lower alkylthio group includes a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, hexylthio, and the like.

[0271] The phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring includes a phenylalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, 2-phenylacetyl, 3-phenylpropionyl, 4-phenylbutyryl, 2,2-dimethyl-3-phenylpropionyl, 5-phenylpentanoyl, 6-phenylhexanoyl, 2-(2-methylphenyl)acetyl, 2-(3-methylphenyl)acetyl, 2-(4-methylphenyl)acetyl, 3-(2-ethylphenyl)propionyl, 2-(3-ethylphenyl)propionyl, 4-(4-ethylphenyl)butyryl, 5-(4-isopropylphenyl)pentanoyl, 6-(3-butylphenyl)hexanoyl, 3-(4-pentylphenyl)propionyl, 2-(4-hexylphenyl)acetyl, 2-(3,4-dimethylphenyl)acetyl, 2-(3,4-diethylphenyl)acetyl, 2-(2,4-dimethylphenyl)acetyl, 2-(2,5-dimethylphenyl)acetyl, 2-(2,6-dimethylphenyl)acetyl, 2-(3,4,5-trimethylphenyl)acetyl, and the like.

[0272] The halogen-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, for example, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxyl, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-bromopropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 5-bromohexyloxy, 5,6-dichlorohexyloxy, and the like.

[0273] The amino-substituted lower alkoxy group having optionally a lower alkyl substituent includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-isopropylaminobutoxy, 4-butylaminobutoxy, 4-tert-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, 2-diethylaminoethoxy, 2-dimethylaminoethoxy, (N-ethyl-N-propylamino)methoxy, 2-(N-methyl-N-hexylamino)ethoxy, and the like.

[0274] The phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent includes a phenyl group which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a hydroxy group, a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, a nitro group, an amino group having optionally a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a phenyl group, and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-propylphenyl, 4-butylphenyl, 2-pentylphenyl, 3-hexylphenyl, 3,4-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 4-ethoxyphenyl, 3-propoxyphenyl, 4-propoxyphenyl, 4-butoxyphenyl, 2-pentyloxyphenyl, 3-hexyloxyphenyl, 2,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2,4-dihydroxyphenyl, 3,4-dihydroxyphenyl, 2,4,6-trihydroxyphenyl, 2-acetyloxyphenyl, 3-propionyloxyphenyl, 2-benzyloxyphenyl, 3-benzyloxyphenyl, 4-benzyloxyphenyl, 2-(2-phenylethoxy)phenyl, 3-(3-phenylpropoxy)phenyl, 4-(4-phenylbutoxy)phenyl, 3-(1-phenylethoxy)phenyl, 2-(5-phenylpentyloxy)phenyl, 3-(6-phenylhexyloxy)phenyl, 2,4-dibenzyloxyphenyl, 3,4-dibenzyloxyphenyl, 3,4,5-tribenzyloxyphenyl, 4-butyryloxyphenyl, 2-pentanoyloxyphenyl, 4-hexanoyloxyphenyl, 2,4-diacetyloxyphenyl, 2,6-diacetyloxyphenyl, 3,4,5-triacetyloxyphenyl, 2-trifluoromethoxyphenyl, 3-(2-chloroethoxy)phenyl, 2-(3-bromopropoxy)phenyl, 4-iodomethoxyphenyl, 2-(2,3-dichloropropoxy)phenyl, 3-(4-fluorobutoxy)phenyl, 4-(3-chloro-2-methylpropoxy)phenyl, 2-(5-bromohexyloxy)phenyl, 3-(5,6-dichlorohexyloxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2,4-bistrifluoromethoxyphenyl, 2,4,6-tri(trifluoromethoxy)phenyl, 2-aminomethoxyphenyl, 3-(1-aminoethoxy)phenyl, 4-(3-aminopropoxy)phenyl, 2-(4-aminobutoxy)phenyl, 3-(5-aminopentyloxy)phenyl, 4-(6-aminohexyloxy)phenyl, 2-methylaminomethoxyphenyl, 3-(2-propylaminoethoxy)phenyl, 2-(3-isopropylaminopropoxy)phenyl, 4-(4-butylaminobutoxy)phenyl, 2-(5-pentylaminopentyloxy)phenyl, 3-(6-hexylaminohexyloxy)phenyl, 4-dimethylaminomethoxyphenyl, 2-(N-ethyl-N-propylaminomethoxy)phenyl, 2-methyl-4-methoxyphenyl, 2-methyl-6-hydroxyphenyl, 4-methyl-2-(3-bromopropoxy)phenyl, 4-methoxy-2-(3-isopropylaminopropoxy)phenyl, 2-phenylphenyl, 3-phenylphenyl, 4-phenylphenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2,3-dinitrophenyl, 2,4,6-trinitrophenyl, 2-aminophenyl, 3-aminophenyl, 4-aminophenyl, 2,4-diaminophenyl, 3,4,5-triaminophenyl, 4-acetylaminophenyl, 2-propionylaminophenyl, 3-butyrylaminophenyl, 4-pentanoylaminophenyl, 4-hexanoylaminophenyl, 2,3-diacetylaminophenyl, 2,4,6-triacetylaminophenyl, and the like.

[0275] The anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes an anilino-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, anilinomethyl, 2-anilinoethyl, 1-anilinoethyl, 3-anilinopropyl, 4-anilinobutyl, 1,1-dimethyl-2-anilinoethyl, 5-anilinopentyl, 6-anilinohexyl, 2-methyl-3-anilinopropyl, (2-methylanilino)methyl, 2-(2-methylanilino)ethyl, 1-(3-methylanilino)ethyl, 3-(4-methylanilino)propyl, 4-(2-ethylanilino)butyl, 5-(3-propylanilino)pentyl, 6-(4-butylanilino)hexyl, 2-(2-pentylanilino)ethyl, 1-(3-hexylanilino)ethyl, 3-(3,4-dimethylanilino)propyl, 2-(3,4,5-trimethylanilino)ethyl, and the like.

[0276] The phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a phenylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which may optionally have 1 to 3 substituents selected from a halogen atom, a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, and an aminocarbonyl group having optionally 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, phenylmethoxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1,1-dimethyl-2-phenylethoxy, 2-methyl-3-phenylpropoxy, (2-chlorophenyl)methoxy, (2-bromophenyl)methoxy, 2-(4-fluorophenyl)ethoxy, 1-(4-bromophenyl)ethoxy, 3-(3-bromophenyl)propoxy, 4-(4-chlorophenyl)butoxy, 5-(2-iodophenyl)pentyloxy, 6-(3-iodophenyl)hexyloxy, (2,6-dichlorophenyl)methoxy, (2,3-dichlorophenyl)methoxy, (2,4-dichlorophenyl)methoxy, (3,4-difluorophenyl)methoxy, (3,4,5-trichlorophenyl)methoxy, (2-methoxycarbonylphenyl)methoxy, (3-ethoxycarbonylphenyl)methoxy, 2-(4-isopropoxycarbonylphenyl)ethoxy, 3-(2-butoxycarbonylphenyl)propoxy, 4-(3-pentyloxycarbonylphenyl)butoxy, 5-(4-hexyloxycarbonylphenyl)pentyloxy, 6-(2-methoxycarbonylphenyl)hexyloxy, (2,4-dimethoxycarbonylphenyl)methoxy, (2,4,6-triethoxycarbonylphenyl)methoxy, (2-carbamoylphenyl)methoxy, 2-(3-methylaminocarbonylphenyl)ethoxy, 1-(4-ethylaminocarbonylphenyl)ethoxy, 3-(2-isopropylaminocarbonylphenyl)propoxy, 4-(3-butylaminocarbonylphenyl)butoxy, 5-(4-pentylaminocarbonylphenyl)pentyloxy, 6-(2-hexylaminocarbonylphenyl)hexyloxy, (2-dimethylaminocarbonylphenyl)methoxy, 2-(3-dibutylaminocarbonylphenyl)ethoxy, 1-(4-dihexylaminocarbonylphenyl)ethoxy, 3-[2-(N-ethyl-N-propylaminocarbonyl)phenyl]propoxy, (2-aminomethylaminocarbonylphenyl)methoxy, 2-[3-(2-aminoethylaminocarbonyl)phenyl]ethoxy, 3-[4-(3-aminopropylaminocarbonyl)phenyl]propoxy, 4-[2-(4-aminobutylaminocarbonyl)phenyl]butoxy, 5-[3-(5-aminopentylaminocarbonyl)phenyl]pentyloxy, 6-[4-(6-aminohexylaminocarbonyl)phenyl]hexyloxy, [2-(N-methyl-N-methylaminomethyl)aminocarbonylphenyl]methoxy, 2-[3-(3-isopropylaminopropylaminocarbonyl)phenyl]ethoxy, 3-{4-[N-propyl-N-(5-pentylaminopentyl)aminocarbonyl]phenyl}propoxy, {2-[N-methyl-N-(2-diethylaminoethyl)aminocarbonyl]phenyl}methoxy, {2-[N,N-bis(diethylaminoethyl)aminocarbonyl]phenyl}methoxy, 4-[3-(N-ethyl-N-propylamino)methylaminocarbonylphenyl]butoxy, 5-[4-{N-[2-(N-methyl-N-hexylamino)ethyl]-N-ethylaminocarbonyl}phenyl]pentyloxy, 6-{4-chloro-2-[N-butyl-N-(6-hexylaminohexyl)aminocarbonyl]phenyl}hexyloxy, [2-bromo-4-(N-hexyl-N-dimethylaminomethyl)aminocarbonylphenyl]methoxy, (2-methoxycarbonyl-3-chlorophenyl)methoxy, and the like.

[0277] The benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring includes a benzoylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which may optionally have 1 to 3 halogen substituents on the phenyl ring, for example, benzoylmethoxy, 2-benzoylethoxy, 1-benzoylethoxy, 3-benzoylpropoxy, 4-benzoylbutoxy, 5-benzoylhexyloxy, 6-benzoylhexyloxy, 1,1-dimethyl-2-benzoylethoxy, 2-methyl-3-benzoylpropoxy, 2-(2-chlorobenzoyl)ethoxy, 1-(3-chlorobenzoyl)ethoxy, (4-chlorobenzoyl)methoxy, 3-(2-fluorobenzoyl)propoxy, 4-(3-fluorobenzoyl)butoxy, 5-(4-fluorobenzoyl)pentyloxy, 6-(2-bromobenzoyl)hexyloxy, 1,1-dimethyl-2-(3-bromobenzoyl)ethoxy, 2-methyl-3-(4-bromobenzoyl)propoxy, (2-iodobenzoyl)methoxy, 2-(3-iodobenzoyl)ethoxy, 3-(4-iodobenzoyl)propoxy, 4-(3,4-dichlorobenzoyl)butoxy, 5-(2,6-dichlorobenzoyl)pentyloxy, 6-(2,3-dichlorobenzoyl)hexyloxy, (2,4-dichlorobenzoyl)methoxy, (3,4-difluorobenzoyl)methoxy, (3,5-dibromobenzoyl)methoxy, (3,4,5-trichlorobenzoyl)methoxy, and the like.

[0278] The phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, which is substituted by a phenyl group having optionally 1 to 3 halogen substituents on the phenyl ring, for example, styryl, 3-phenyl-2-propenyl, 3-phenyl-1-propenyl, 4-phenyl-3-butenyl, 4-phenyl-2-butenyl, 4-phenyl-1-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 5-phenyl-2-pentenyl, 5-phenyl-1-pentenyl, 1-methyl-3-phenyl-2-butenyl, 6-phenyl-5-hexenyl, 1-methylstyryl, 2-, 3- or 4-chlorostyryl, 3-(4-bromophenyl)-2-propenyl, 3-(3-fluorophenyl)-1-propenyl, 4-(4-iodophenyl)-3-butenyl, 5-(2-chlorophenyl)-4-pentenyl, 2-methyl-3-bromostyryl, 3,4-dichlorostyryl, 3,4,5-trichlorostyryl, and the like.

[0279] The benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a benzoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, benzoylmethyl, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 1,1-dimethyl-2-benzoylethyl, 5-benzoylpentyl, 6-benzoylhexyl, 2-methyl-3-benzoylpropyl, 2-(methylbenzoyl)methyl, 2-(2-methylbenzoyl)ethyl, 1-(3-methylbenzoyl)ethyl, 3-(4-methylbenzoyl)propyl, 4-(2-ethylbenzoyl)butyl, 5-(3-propylbenzoyl)pentyl, 6-(4-butylbenzoyl)hexyl, 2-(2-pentylbenzoyl)ethyl, 1-(3-hexylbenzoyl)ethyl, 3-(3,4-dimethylbenzoyl)propyl, 2-(3,4,5-trimethylbenzoyl)ethyl, and the like.

[0280] The pyrrolidinyl-substituted lower alkoxy group includes a pyrrolidinylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrrolidinyl)methoxy, 2-(2-pyrrolidinyl)ethoxy, 1-(3-pyrrolidinyl)ethoxy, 3-(2-pyrrolidinyl)propoxy, 4-(3-pyrrolidinyl)butoxy, 5-(2-pyrrolidinyl)pentyloxy, 6-(3-pyrrolidinyl)hexyloxy, 1,1-dimethyl-2-(2-pyrrolidinyl)ethoxy, 2-methyl-3-(3-pyrrolidinyl)propoxy, 5-(1-pyrrolidinyl)pentyloxy, 2-(1-pyrrolidinyl)ethoxy, and the like.

[0281] The phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, 2-methylbenzyl, 2-(2-methylphenyl)ethyl, 1-(3-methylphenyl)ethyl, 3-(4-methylphenyl)propyl, 4-(2-ethylphenyl)butyl, 5-(3-propylphenyl)pentyl, 6-(4-butylphenyl)hexyl, 2-(2-pentylphenyl)ethyl, 1-(3-hexylphenyl)ethyl, 3-(3,4-dimethylphenyl)propyl, 2-(3,4,5-trimethylphenyl)ethyl, (2-methyl-6-chlorophenyl)methyl, and the like.

[0282] The lower alkoxycarbonyl group includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyoxycarbonyl, and the like.

[0283] The aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent includes an aminocarbonyl group which may optionally have 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl, pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, aminomethylaminocarbonyl, 2-aminoethylaminocarbonyl, 1-aminoethylaminocarbonyl, 3-aminopropylaminocarbonyl, 4-aminobutylaminocarbonyl, 5-aminopentylaminocarbonyl, 6-aminohexylaminocarbonyl, 1,1-dimethyl-2-aminoethylaminocarbonyl, 2-methyl-3-aminopropylaminocarbonyl, methylaminomethylaminocarbonyl, 1-ethylaminoethylaminocarbonyl, 2-propylaminoethylaminocarbonyl, 3-isopropylaminopropylaminocarbonyl, 4-butylaminobutylaminocarbonyl, 5-pentylaminopentylaminocarbonyl, 6-hexylaminohexylaminocarbonyl, dimethylaminomethylaminocarbonyl, 2-diethylaminoethylaminocarbonyl 2-dimethylaminoethylaminocarbonyl, (N-ethyl-N-propylamino)methylaminocarbonyl, 2-(N-methyl-N-hexylamino)ethylaminocarbonyl, N-methyl-N-(2-diethylaminoethyl)aminocarbonyl, N-ethyl-N-(methylaminomethyl)aminocarbonyl, and the like.

[0284] The lower alkyl group having optionally a hydroxy substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally have 1 to 3 hydroxy substituents, for example, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, and the like.

[0285] The carbamoyl-lower alkyl group includes a carbamoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carbamoylmethyl, 2-carbamoylethyl, 1-carbamoylethyl, 3-carbamoylpropyl, 4-carbamoylbutyl, 5-carbamoylpentyl, 6-carbamoylhexyl, 1,1-dimethyl-2-carbamoylethyl, 2-methyl-3-carbamoylpropyl, and the like.

[0286] The adamantyl-substituted lower alkyl group includes an adamantyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, adamantylmethyl, 2-adamantylethyl, 1-adamantylethyl, 3-adamantylpropyl, 4-adamantylbutyl, 5-adamantylpentyl, 6-adamantylhexyl, 1,1-dimethyl-2-adamantylethyl, 2-methyl-3-adamantylpropyl, and the like.

[0287] The lower alkylsulfonyl group includes an alkylsulfonyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, and the like.

[0288] The hydroxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which have 1 to 3 hydroxy substituents, for example, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, and the like.

[0289] The phenyl-lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by 1 to 2 phenyl groups, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1,1-dimethyl-2-phenylethyl, 2-methyl-3-phenylpropyl, diphenylmethyl, 2,2-diphenylethyl, and the like.

[0290] The quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring includes, for example, quinolylcarbonyl, 2-phenylquinolylcarbonyl, 3-phenylquinolylcarbonyl, 4-phenylquinolylcarbonyl, 5-phenylquinolylcarbonyl, 6-phenylquinolylcarbonyl, 7-phenylquinolylcarbonyl, 8-phenylquinolylcarbonyl, and the like.

[0291] The thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring includes, for example, thienylcarbonyl, 2-phenylthienylcarbonyl, 3-phenylthienylcarbonyl, 4-phenylthienylcarbonyl, and the like.

[0292] The thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring includes, for example, thiazolylcarbonyl, 2-phenylthiazolylcarbonyl, 4-phenylthiazolylcarbonyl, 5-phenylthiazolylcarbonyl, and the like.

[0293] The cycloalkylcarbonyl group includes a cycloalkylcarbonyl group having 3 to 8 carbon atoms in the cycloalkyl moiety, for example, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, and the like.

[0294] The lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms which may optionally have 1 to 3 substituents selected from a halogen atom and a hydroxy group, for example, in addition to the above-mentioned lower alkanoyl groups having optionally a halogen substituent, 2-hydroxyacetyl, 3-hydroxypropionyl, 2-hydroxypropionyl, 4-hydroxybutyryl, 5-hydroxypentanoyl, 6-hydroxyhexanoyl, 2,2-dimethyl-3-hydroxypropionyl, and the like.

[0295] The halogen-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, for example, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-bromopropyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, and the like.

[0296] The amino group having optionally a lower alkyl substituent includes an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, and the like.

[0297] The lower alkoxycarbonyl group having optionally a halogen substituent includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, which may optionally have 1 to 3 halogen substituents, for example, in addition to the above-mentioned lower alkoxycarbonyl groups, trifluoromethoxycarbonyl, trichloromethoxycarbonyl, chloromethoxycarbonyl, bromomethoxycarbonyl, fluoromethoxycarbonyl, iodomethoxycarbonyl, difluoromethoxycarbonyl, dibromomethoxycarbonyl, 2-chloroethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 3-bromopropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxycarbonyl, 4-fluorobutoxycarbonyl, 5-chloropentyloxycarbonyl, 3-chloro-2-methylpropoxycarbonyl, 5-bromohexyloxycarbonyl, 5,6-dichlorohexyloxycarbonyl, and the like.

[0298] The lower alkoxy-substituted lower alkanoyl group includes an alkoxyalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms and the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, 2-methoxyacetyl, 3-methoxypropionyl, 2-ethoxyacetyl, 3-ethoxypropionyl, 4-ethoxybutyryl, 3-propoxypropionyl, 2-methoxypropionyl, 6-propoxyhexanoyl, 5-isopropoxypentanoyl, 2,2-dimethyl-3-butoxypropionyl, 2-methyl-3-tert-butoxypropionyl, 2-pentyloxyacetyl, 2-hexyloxyacetyl, and the like.

[0299] The lower alkanoyloxy-substituted lower alkanoyl group includes an alkanoyloxyalkanoyl group wherein the alkanoyl moieties are a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, 2-acetyloxyacetyl, 3-acetyloxypropionyl, 2-propionyloxyacetyl, 3-propionyloxypropionyl, 4-propionyloxybutyryl, 3-butyryloxypropionyl, 2-acetyloxypropionyl, 6-propionyloxyhexanoyl, 5-butyryloxypentanoyl, 2,2-dimethyl-3-butyryloxypropionyl, 2-pentanoyloxyacetyl, 2-hexanoyloxyacetyl, and the like.

[0300] The quinolyloxy-substituted alkanoyl group includes a quinolyloxyalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2-quinolyloxyacetyl, 3-quinolyloxypropionyl, 2-quinolyloxypropionyl, 4-quinolyloxybutyryl, 2,2-dimethyl-3-quinolyloxypropionyl, 5-quinolyloxypentanoyl, 6-quinolyloxyhexanoyl, and the like.

[0301] The phenyl-lower alkoxycarbonyl group includes a phenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, 5-phenylpentyloxycarbonyl, 6-phenylhexyloxycarbonyl, 1,1-dimethyl-2-phenylethoxycarbonyl, 2-methyl-3-phenylpropoxycarbonyl, and the like.

[0302] The benzoyl-lower alkyl group includes a benzoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzoylmethyl, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 5-benzoylpentyl, 6-benzoylhexyl, 1,1-dimethyl-2-benzoylethyl, 2-methyl-3-benzoylpropyl, and the like.

[0303] The tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring includes a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, which is substituted by a tetrahydroquinolyloxy group having optionally 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and an oxo group on the quinoline ring, for example, 2-tetrahydroquinolyloxyacetyl, 3-tetrahydroquinolyloxypropionyl, 2-tetrahydroquinolyloxypropionyl, 4-tetrahydroquinolyloxybutyryl, 2,2-dimethyl-3-tetrahydroquinolyloxypropionyl, 5-tetrahydroquinolyloxypentanoyl, 6-tetrahydroquinolyloxyhexanoyl, 2-(1-methyltetrahydroquinolyloxy)acetyl, 2-(2-oxotetrahydroquinolyloxy)acetyl, 3-(2-ethyltetrahydroquinolyloxy)propionyl, 2-(3-propyltetrahydroquinolyloxy)propionyl, 4-(4-butyltetrahydroquinolyloxy)butyryl, 2,2-dimethyl-3-(5-pentyltetrahydroquinolyloxy)propionyl, 5-(6-hexyltetrahydroquinolyloxy)pentanoyl, 6-(7-methyltetrahydroquinolyloxy)hexanoyl, 2-(8-methyltetrahydroquinolyloxy)acetyl, 2-(1,4-dimethyltetrahydroquinolyloxy)acetyl, 2-(2,4,6-trimethyltetrahydroquinolyloxy)acetyl, 2-(1-methyl-2-oxotetrahydroquinolyloxy)acetyl, 3-(2-oxotetrahydroquinolyloxy)propionyl, 4-(2-oxotetrahydroquinolyloxy)butyryl, 5-(2-oxotetrahydroquinolyloxy)pentanoyl, 6-(2-oxotetrahydroquinolyloxy)hexanoyl, 2-(1,6-dimethyl-2-oxotetrahydroquinolyloxy)acetyl, and the like.

[0304] The tetrahydronaphthyloxy-lower alkanoyl group includes a tetrahydronaphthyloxyalkanoyl group wherein the alkanoyl group is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atom, for example, 2-tetrahydronaphthyloxyacetyl, 3-tetrahydronaphthyloxypropionyl, 2-tetrahydronaphthyloxypropionyl, 4-tetrahydronaphthyloxybutyryl, 2,2-dimethyl-3-tetrahydronaphthyloxypropionyl, 5-tetrahydronaphthyloxypentanoyl, 6-tetrahydronaphthyloxyhexanoyl, and the like.

[0305] The phenyl-lower alkenylcarbonyl group includes a phenylalkenylcarbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms in the alkenyl moiety, for example cinnamoyl, 3-phenyl-2-propenylcarbonyl, 3-phenyl-1-propenylcarbonyl, 4-phenyl-3-butenylcarbonyl, 4-phenyl-2-butenylcarbonyl, 4-phenyl-1-butenylcarbonyl, 5-phenyl-4-pentenylcarbonyl, 5-phenyl-3-pentenylcarbonyl, 5-phenyl-2-pentenylcarbonyl, 5-phenyl-1-pentenylcarbonyl, 1-methyl-3-phenyl-2-butenylcarbonyl, 1-methylcinnamoyl, and the like.

[0306] The cycloalkenyl group includes a cycloalkenyl group having 3 to 8 carbon atoms, for example, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and the like.

[0307] The phenyl-lower alkylaminocarbonyl group includes a phenylalkylaminocarbonyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzylaminocarbonyl, (2-phenylethyl)aminocarbonyl, (1-phenylethyl)aminocarbonyl, (3-phenylpropyl)aminocarbonyl, (4-phenylbutyl)aminocarbonyl, (5-phenylpentyl)aminocarbonyl, (6-phenylhexyl)aminocarbonyl, (1,1-dimethyl-2-phenylethyl)aminocarbonyl, (2-methyl-3-phenylpropyl)aminocarbonyl, and the like.

[0308] The 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyridyl, homopiperazinyl, 1,2,5,6-tetrahydropyridyl, thienyl, quinolyl, 1,4-dihydroquinolyl, benzothiazolyl, pyrazyl, pyrimidyl, pyridazyl, pyrrolyl, carbostyril, 3,4-dihydrocarbostyril, 1,2,3,4-tetrahydroquinolyl, indolyl, isoindolyl, indolinyl, benzimidazolyl, benzoxazolyl, imidazolidinyl, isoquinolyl, quinazolidinyl, 1,2,3,4-tetrahydroquinolyl, 1,2-dihydroisoquinolyl, quinoxalinyl, cinnolinyl, phthalazinyl, 1,2,3,4-tetrazolyl, 1,2,4-triazolyl, chromanyl, isoindolinyl, isochromanyl, pyrazolyl, imidazolyl, pyrazolidinyl, imidazo[1,2-a]pyridyl, benzofuryl, 2,3-dihydrobenzo[b]furyl, benzothienyl, 1-azacycloheptyl, 4H-chromenyl, 1H-indazolyl, isoindolinyl, 2-imidazolinyl, 2-pyrrolinyl, furyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, pyranyl, pyrazolidinyl, 2-pyrazolinyl, quinuclidinyl, 1,4-benzoxazinyl, 3,4-dihydro-2H-1,4-benzoxazinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 1,4-benzothiadinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dithia-2,4-dihydronaphthalenyl, tetrahydro-1,3-oxazinyl, tetrahydrooxazolyl, 1,4-dithianaphthalenyl, and the like.

[0309] The above-mentioned heterocyclic group having 1 to 3 substituents selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group includes the above-mentioned heterocyclic groups having 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenyl group, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a halogen atom, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and an oxo group, for example, 1-oxo-1,2,3,4-tetrahydroisoquinolyl, 2-oxopiperidinyl, 2-oxo-1-azabicycloheptyl, 2-oxopyrrolidinyl, 5-phenylthiazolyl, 1-methylimidazolyl, 1-propylimidazolyl, 4-methylimidazolyl, 4-phenylimidazolyl, 1,4-dimethylpyrrolyl, 4-methylpiperazinyl, 4-phenylpiperidinyl, 4-methylthiazolyl, 2-oxothiazolyl, 5-ethylthiazolyl, 4-phenylthiazolyl, 4-propylthiazolyl, 5-butylthiazolyl, 4-pentylthiazolyl, 2-hexylthiazolyl, 4,5-dimethylthiazolyl, 5-phenyl-4-methylthiazolyl, 1-ethylimidazolyl, 4-propylimidazolyl, 5-butylimidazolyl, 1-pentylimidazolyl, 1-hexylimidazolyl, 1,4-dimethylimidazolyl, 1,4,5-trimethylimidazolyl, 1-phenylimidazolyl, 2-phenylimidazolyl, 5-phenylimidazolyl, 1-methyl-4-phenylimidazolyl, 3-methyl-1,2,4-triazolyl, 5-ethyl-1,2,4-triazolyl, 3-phenyl-1,2,4-triazolyl, 2-oxo-1-methylimidazolyl, 2-oxoimidazolyl, 2-ethylpyrrolyl, 3-propylpyrrolyl, 5-butylpyrrolyl, 4-pentylpyrrolyl, 2-hexylpyrrolyl, 2,4,5-trimethylpyrrolyl, 2-phenylpyrrolyl, 2,5-diphenylpyrrolyl, 2-methyl-5-phenylpyrrolyl, 2-oxopyrrolyl, 1-methyl-1,2,3,4-tetrazolyl, 1-phenyl-1,2,3,4-tetrazolyl, 1-ethyl-1,2,3,4-tetrazolyl, 1-propyl-1,2,3,4-tetrazolyl, 1-butyl-1,2,3,4-tetrazolyl, 1-pentyl-1,2,3,4-tetrazolyl, 1-hexyl-1,2,3,4-tetrazolyl, 1-phenyl-1,2,3,4-tetrazolyl, 2-methylpyridyl, 3-ethylpyridyl, 4-propylpyridyl, 2-butylpyridyl, 3-pentylpyridyl, 4-hexylpyridyl, 2-phenylpyridyl, 3-phenylpyridyl, 4-phenylpyridyl, 2,4-dimethylpyridyl, 2,4,6-trimethylpyridyl, 2-methyl-4-phenylpyridyl, 2,4-diphenylpyridyl, 2,4,6-triphenylpyridyl, 2-oxopyridyl, 4-oxopyridyl, 4-methyl-2-oxopyridyl, 2-phenyl-4-oxopyridyl, 3-methylimidazo[1,2-a]pyridyl, 4-ethylimidazo[1,2-a]pyridyl, 3-phenylimidazo[1,2-a]pyridyl, 5-phenylimidazo[1,2-a]-pyridyl, 3-methyl-1H-indazolyl, 3-phenyl-1H-indazolyl, 1-methyl-1,2,3,4-tetrahydroisoquinolyl, 5-ethyl-1,2,3,4-tetrahydroisoquinoly, 6-phenyl-1,2,3,4-tetrahydroisoquinolyl, 1-oxo-6-methyl-1,2,3,4-tetrahydroisoquinolyl, 1-oxo-7-phenyl-1,2,3,4-tetrahydroisoquinolyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 1-methylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 4-pentylmorpholino, 4-hexylpiperazinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-hexylpiperazinyl, 3-methylthiomorpholino, 4-phenylpiperazinyl, 3-phenylpyrrolidinyl, 2-oxo-4-methylpiperidinyl, 2-oxo-3-methylpyrrolidinyl, 2-oxo-4-phenylpiperidinyl, 4-methyl-1-azabicycloheptyl, 5-phenyl-1-azacycloheptyl, 6-methyl-2-oxo-1-azacycloheptyl, 1-methyl-2-oxoimidazolidinyl, 1-isobutyl-2-oxoimidazolidinyl, 1-benzyl-2-oxoimidazolidinyl, 2-oxotetrahydro-1,3-oxazinyl, 3-phenyl-2-oxo-1-azacycloheptyl, 2-oxotetrahydrooxazolyl, 3-chloropyridyl, 4-methylpiperazinyl, 4-isobutylpiperazinyl, 4-methylhomopiperazinyl, 4-acetylpiperazinyl, 4-benzylpiperazinyl, 4-ethylhomopiperazinyl, and the like.

[0310] The cyano-substituted lower alkyl group includes a cyanoalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1,1-dimethyl-2-cyanoethyl, 2-methyl-3-cyanopropyl, and the like.

[0311] The tetrazolyl-substituted lower alkyl group includes a tetrazolylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, tetrazolylmethyl, 2-tetrazolylethyl, 1-tetrazolylethyl, 3-tetrazolylpropyl, 4-tetrazolylbutyl, 5-tetrazolylpentyl, 6-tetrazolylhexyl, 1,1-dimethyl-2-tetrazolylethyl, 2-methyl-3-tetrazolylpropyl, and the like.

[0312] The lower alkanoyloxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, acetyoxymethyl, 2-propionyloxyethyl, 1-butyryloxyethyl, 3-acetyloxypropyl, 4-acetyloxybutyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl, 6-acetyloxyhexyl, 6-tert-butylcarbonyloxyhexyl, 1,1-dimethyl-2-hexanoyloxyethyl, 2-methyl-3-acetyloxypropyl, and the like.

[0313] The amino group having optionally a lower alkanoyl substituent includes an amino group having optionally a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like.

[0314] The pyridyl-lower alkyl group includes a pyridylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (4-pyridyl)methyl, 1-(3-pyridyl)ethyl, 2-(2-pyridyl)ethyl, 3-(2-pyridyl)propyl, 4-(3-pyridyl)butyl, 5-(4-pyridyl)pentyl, 6-(2-pyridyl)hexyl, 1,1-dimethyl-2-(3-pyridyl)ethyl, 2-methyl-3-(4-pyridyl)propyl, and the like.

[0315] The phenoxy-lower alkoxycarbonyl group includes a phenoxyalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, phenoxymethoxycarbonyl, 2-phenoxyethoxycarbonyl, 1-phenoxyethoxycarbonyl, 3-phenoxypropoxycarbonyl, 4-phenoxybutoxycarbonyl, 5-phenoxypentyloxycarbonyl, 6-phenoxyhexyloxycarbonyl, 1,1-dimethyl-2-phenoxyethoxycarbonyl, 2-methyl-3-phenoxypropoxycarbonyl, and the like.

[0316] The pyridyl-lower alkoxycarbonyl group includes a pyridylalkoxycarbonyl group wherein the alkoxycarbonyl group is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, (4-pyridyl)methoxycarbonyl, (2-pyridyl)methoxycarbonyl, (3-pyridyl)methoxycarbonyl, 2-(2-pyridyl)ethoxycarbonyl, 1-(1-pyridyl)ethoxycarbonyl, 3-(3-pyridyl)propoxycarbonyl, 4-(4-pyridyl)butoxycarbonyl, 5-(3-pyridyl)pentyloxycarbonyl, 6-(2-pyridyl)hexyloxycarbonyl, 1,1-dimethyl-2-(4-pyridyl)ethoxycarbonyl, 2-methyl-3-(3-pyridyl)propoxycarbonyl, and the like.

[0317] The fluorenyl-lower alkoxycarbonyl group includes a fluorenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, (5-fluorenyl)methoxycarbonyl, 2-(2-fluorenyl)ethoxycarbonyl, 1-(1-fluorenyl)ethoxycarbonyl, 3-(3-fluorenyl)propoxycarbonyl, 4-(4-fluorenyl)butoxycarbonyl, 5-(5-fluorenyl)pentyloxycarbonyl, 6-(1-fluorenyl)hexyloxycarbonyl, 1,1-dimethyl-2-(2-fluorenyl)ethoxycarbonyl, 2-methyl-3-(3-fluorenyl)propoxycarbonyl, and the like.

[0318] The lower alkenyloxycarbonyl group includes an alkenyloxycarbonyl group wherein the alkenyloxycarbonyl moiety is a straight chain or branched chain alkenyloxycarbonyl group having 2 to 6 carbon atoms in the alkenyloxy moiety, for example, vinyloxycarbonyl, allyloxycarbonyl, 2-butenyloxycarbonyl, 3-butenyloxycarbonyl, 1-methylallyloxycarbonyl, 2-pentenyloxycarbonyl, 2-hexenyloxycarbonyl.

[0319] The piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring includes a piperidinylalkoxycarbonyl group wherein the alkoxycarbonyl group is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, which may have optionally 1 to 3 substituents selected from a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (4-piperidinyl)methoxycarbonyl, 2-(3-piperidinyl)ethoxycarbonyl, 1-(2-piperidinyl)ethoxycarbonyl, 3-(1-piperidinyl)propoxycarbonyl, 4-(4-piperidinyl)butoxycarbonyl, 5-(3-piperidinyl)pentyloxycarbonyl, 6-(2-piperidinyl)hexyloxycarbonyl, 1,1-dimethyl-2-(4-piperidinyl)ethoxycarbonyl, 2-methyl-3-(1-piperidinyl)propoxycarbonyl, (1-ethyl-4-piperidinyl)methoxycarbonyl, (1-t-butoxycarbonyl-4-piperidinyl)methoxycarbonyl, (1-acetyl-4-piperidinyl)methoxycarbonyl, 2-(1-methyl-4-piperidinyl)ethoxycarbonyl, 1-(4-propyl-2-piperidinyl)ethoxycarbonyl, 3-(4-butyl-3-piperidinyl)propoxycarbonyl, 4-(3-pentyl-2-piperidinyl)butoxycarbonyl, 5-(1-hexyl-4-piperidinyl) pentyloxycarbonyl, (1,2-dimethyl-4-piperidinyl)methoxycarbonyl, (3,4,5-trimethyl-1-piperidinyl)methoxycarbonyl, 2-(1-methoxycarbonyl-4-piperidinyl)ethoxycarbonyl, 1-(1-ethoxycarbonyl-4-piperidinyl)ethoxycarbonyl, 3-(4-propoxycarbonyl-1-piperidinyl)propoxycarbonyl, 4-(3-pentyloxycarbonyl-2-piperidinyl)butoxycarbonyl, 5-(1-hexyloxycarbonyl-4-piperidinyl)pentyloxycarbonyl, 6-(4-methoxycarbonyl-1-piperidinyl)hexyoxycarbonyl, 2-(2-acetyl-1-piperidinyl)ethoxycarbonyl, 1-(3-propionyl-2-piperidinyl)ethoxycarbonyl, 3-(4-butyryl-3-piperidinyl)propoxycarbonyl, 4-(4-pentanoyl-1-piperidinyl)butoxycarbonyl, 5-(1-hexanoyl-4-piperidinyl)pentyloxycarbonyl, 6-(1-acetyl-2-methyl-4-piperidinyl)hexyoxycarbonyl, (1-ethoxycarbonyl-2,6-dimethyl-4-piperidinyl)methoxycarbonyl, and the like.

[0320] The aminosulfonyloxy group having optionally a lower alkyl substituent includes an aminosulfonyloxy group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminosulfonyloxy, methylaminosulfonyloxy, ethylaminosulfonyloxy, propylaminosulfonyloxy, isopropylaminosulfonyloxy, butylaminosulfonyloxy, tert-butylaminosulfonyloxy, pentylaminosulfonyloxy, hexylaminosulfonyloxy, dimethylaminosulfonyloxy, diethylaminosulfonyloxy, dipropylaminosulfonyloxy, dibutylaminosulfonyloxy, dipentylaminosulfonyloxy, dihexylaminosulfonyloxy, N-methyl-N-ethylaminosulfonyloxy, N-ethyl-N-propylaminosulfonyloxy, N-methyl-N-butylaminosulfonyloxy, N-methyl-N-hexylaminosulfonyloxy, and the like.

[0321] The phenyl-lower alkyl group includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, and the like.

[0322] The lower alkanoyl-substituted amino group includes an amino group substituted by a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butycarbonylamino, hexanoylamino, and the like.

[0323] The benzoheterocyclic derivatives of the present invention can be prepared by the following processes.

[0324] wherein G, R¹, R², R³, R and X are the same as defined above.

[0325] The process of Reaction Scheme-1 is carried out by reacting a benzoheterocyclic compound [2] and a carboxylic acid compound [3] by the conventional amido bond producing reaction. The amido bond producing reaction can be carried out under the conditions for the conventional amido bond producing reaction, for example,

[0326] (a) a mixed acid anhydride process, i.e. a process of reacting the carboxylic acid compound [3] with an alkyl carbonate to form a mixed acid anhydride and reacting the resultant with the amine compound [2],

[0327] (b) an activated ester process, i.e. a process of converting the carboxylic acid compound [3] into an activated ester such as p-nitrophenyl ester, N-hydroxysuccinimide ester, 1-hydroxybenzotriazole ester, etc., and reacting the resultant with the amine compound [2],

[0328] (c) a carbodiimide process, i.e. a process of condensing the carboxylic acid compound [3] and the amine compound [2] in the presence of an activating agent such as dicyclohexylcarbodiimide, carbonyldiimidazole, etc.,

[0329] (d) other processes, i.e. a process of converting the carboxylic acid compound [3] into a carboxylic anhydride by treating it with a dehydrating agent such as acetic anhydride, and reacting the resultant with the amine compound [2]; a process of reacting an ester of the carboxylic acid compound [3] with a lower alcohol and the amine compound [2] at a high temperature under high pressure; a process of reacting an acid halide compound of the carboxylic acid compound [3], i.e. a carboxylic acid halide, with the amine compound [2], and the like.

[0330] The mixed acid anhydride used in the above mixed acid anhydride process (a) is obtained by the known Schotten-Baumann reaction, and the reaction product is used without isolating from the reaction mixture for the reaction with the amine compound [2] to give the desired compound [1] of the present invention. The above Schotten-Baumann reaction is usually carried out in the presence of a basic compound. The basic compound is any conventional compounds used in the Schotten-Baumann reaction and includes, for example, organic basic compounds such as triethylamine, trimethylamine, pyridine, dimethylaniline, 1-methyl-2-pyrrolidine (NMP), N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), and inorganic basic compounds such as potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, etc. The reaction is usually carried out at a temperature from about −20° C. to about 100° C., preferably at a temperature from 0° C. to about 50° C., for about 5 minutes to about 10 hours, preferably for 5 minutes to about 2 hours.

[0331] The reaction between the mixed acid anhydride thus obtained and the amine compound [2] is usually carried out at a temperature from −20° C. to about 150° C., preferably at a temperature from 10° C. to about 50° C., for 5 minutes to about 10 hours, preferably for 5 minutes to about 5 hours. The mixed acid anhydride process is usually carried out in a solvent. The solvent may be any conventional solvents which are usually used in the mixed acid anhydride process and includes, for example, halogenated hydrocarbons (e.g. chloroform, dichloromethane, dichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, p-chlorobenzene, toluene, xylene, etc.), ethers (e.g. diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. methyl acetate, ethyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, acetonitrile, hexamethylphosphoric triamide, etc.), or a mixture of these solvents. The alkyl halocarbonate used in the mixed acid anhydride process includes, for example, methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate, isobutyl chloroformate, and the like. In said process, the carboxylic acid compound [3], the alkyl halocarbonate and the amine compound [2] are usually used in each equimolar amount, but preferably, the alkyl halocarbonate and the carboxylic acid compound [3] are used each in an amount of about 1 to 1.5 mole to 1 mole of the amine compound [2].

[0332] Among the above other processes (d), in case of the process of reacting the carboxylic acid halide with the amine compound [2], the reaction is usually carried out in the presence of a basic compound in an appropriate solvent. The basic compound is any conventional compounds and includes, for example, in addition to the basic compounds used in the above Schötten-Baumann reaction, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, and the like. The solvent includes, for example, in addition to the solvents used in the mixed acid anhydride process, alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.), pyridine, acetone, water, and the like. The amount of the amine compound [2] and the carboxylic acid halide is not critical, but the carboxylic acid halide is usually used at least in equimolar amount, preferably about in an amount of 1 mole to 5 moles to 1 mole of the amine compound [2]. The reaction is usually carried out at a temperature from about −20° C. to about 180° C., preferably at a temperature from 0° C. to about 150° C., for about 5 minutes to about 30 hours.

[0333] The amido bond producing reaction in above Reaction Scheme-1 may also be carried out by reacting the carboxylic acid compound [3] and the amine compound [2] in the presence of a condensing agent such as phosphorus compounds (e.g. phenylphosphine-2,2′-dithiodipyridine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, diphenylphosphoric azide, bis(2-oxo-3-oxazolidinyl)phosphinic chloride, etc.).

[0334] The reaction is usually carried out in the presence of the solvent and the basic compound as used in the above reaction of the carboxylic acid halide and the amine compound [2] at a temperature from −20° C. to 150° C., preferably at a temperature from 0° C. to about 100° C., for about 5 minutes to about 30 hours. The condensing agent and the carboxylic acid compound [3] are used at least in an equimolar amount, preferably in an amount of about 1 to 2 moles, to 1 mole of the amine compound [2].

[0335] wherein G, p, R¹, R², R³, R⁸ and X are the same as defined above, R^(10a) is a hydrogen atom, a lower alkyl group or a lower alkanoyl group having optionally a halogen substituent, R^(11a) is a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom, wherein the alkanoyl moiety may optionally be substituted by a halogen atom, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a group of the formula:

[0336] a phenoxy-lower alkoxycarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, a lower alkoxycarbonyl group having optionally a halogen substituent, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a tetrahydroisoquinolylcarbonyl group, a phenyl-lower alkoxycarbonyl group or a phenyl-lower alkenylcarbonyl group, R^(11b) is a lower alkyl group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, wherein the alkyl moiety may optionally be substituted by a hydroxy group, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a benzoyl-lower alkyl group or a lower alkylsulfonyl group, X¹ is a halogen atom, M is an alkali metal such as sodium, potassium, etc., and R¹⁵ is a lower alkyl group, a pyridyl-lower alkyl group or a phenyl-lower alkyl group.

[0337] The reaction of the compound [4] and the compound [5] is carried out in the same conditions as in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.

[0338] The reaction of the compound [4] and the compound [6a] is usually carried out in the presence or absence of a basic compound in an appropriate inert solvent. The inert solvent includes, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. tetrahydrofuran, dioxane, diethylene glycol dimethyl ether, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, butanol, t-butanol, etc.), acetic acid, ethyl acetate, acetone, acetonitrile, pyridine, dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, or a mixture of these solvents. The basic compound includes, for example, carbonates or hydrogen carbonates of alkali metal (e.g. sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc.), metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, etc.), sodium hydride, potassium, sodium, sodium amide, metal alcoholates (e.g. sodium methylate, sodium ethylate, etc.), or organic basic compounds such as pyridine, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO). The amount of the compound [4] and the compound [6a] is not critical, but the compound [6a] is usually used at least in an equimolar amount, preferably in an amount of 1 to 10 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from 0° C. to about 200° C., preferably at a temperature from 0° C. to about 170° C., for 30 minutes to about 75 hours. There may be added an alkali metal halide such as sodium iodide, potassium iodide, copper powder, etc. into the reaction system.

[0339] The reaction of the compound [4] and the compound [6b] is carried out under the same condition as in the reaction of the compound [1t] and the compound [18] in the following Reaction Scheme-9.

[0340] The reaction of the compound [4] and the compound [7] is carried out in the presence of an acid in an appropriate solvent. The acid includes, for example, organic acids (e.g. acetic acid, trifluoroacetic acid, etc.), or inorganic acids (e.g. hydrochloric acid, sulfuric acid, etc.). The solvent may be the same solvents as those used in the reaction of the carboxylic acid halide and the amine compound [2] in above Reaction Scheme-1. The compound [71 is used at least in an equimolar amount, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is carried out at a temperature from 0° C. to about 150° C., preferably at a temperature from room temperature to about 100° C., for 10 minutes to about 5 hours.

[0341] The reaction of the compound [4] and the compound [8] is carried out in the presence or absence of a basic compound, preferably in the absence of a basic compound, in an appropriate solvent or without a solvent. The solvent and the basic compound used therein are the same ones as those used in the reaction of the carboxylic acid halide and the amine compound [2] in above Reaction Scheme-1.

[0342] The compound [8] is usually used at least in an amount of 1 to 5 moles, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from 0° C. to about 200° C., preferably at a temperature from room temperature to 150° C., for 5 minutes to about 30 hours. There may be added a boron compound such as boron trifluoride ethyl ether, etc. into the reaction system.

[0343] wherein R¹ and R are the same as defined above, G^(a) is a group of the formula:

[0344] or a group of the formula:

[0345] G_(b) is a group of the formula:

[0346] or a group of the formula:

[0347] G_(c) is a group of the formula:

[0348] or a group of the formula:

[0349] and X, Y, R⁴ and R⁵ are the same as defined above.

[0350] The reaction of converting the compound [1e] into the compound [1f] is carried out by reduction. The reduction reaction is carried out by using a hydrogenating agent. The hydrogenating agent includes, for example, lithium aluminum hydride, lithium borohydride, sodium borohydride, diboran, etc., and is used at least in an equimolar amount, preferably in an amount of 1 to 15 moles, to 1 mole of the starting compound. The reduction reaction is usually carried out in an appropriate solvent such as water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.), or a mixture of these solvents. The reduction is usually carried out at a temperature from about −60° C. to 150° C., preferably at a temperature from −30° C. to 100° C., for about 10 minutes to 15 hours. When lithium aluminum hydride or diboran is used as a reducing agent, the reaction is preferably carried out in an anhydrous solvent such as tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.

[0351] The reaction of converting the compound [1e] into the compound [1g] is carried out in an appropriate solvent or without a solvent in the presence or absence of a dehydrating agent. The solvent includes, for example, alcohols (e.g. methanol, ethanol, isopropanol, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), aprotic polar solvents (e.g. dimethylformamide, dimethylacetamide, N-methylpyrrolidone, etc.), or a mixture of these solvents. The dehydrating agent includes, for example, drying agents which are conventionally used for drying solvents (e.g. molecular sieves, etc.), mineral acids (e.g. hydrochloric acid, sulfuric acid, boron trifluoride, etc.), organic acids (e.g. p-toluenesulfonic acid, acetic acid, etc.). The reaction is usually carried out at a temperature from room temperature to 250° C., preferably at a temperature from about 50° C. to about 200° C., for one to about 48 hours. The amount of the compound [9] is not critical, but it is used at least in an equimolar amount, preferably in an amount of 1 mole to excess amount, to 1 mole of the compound [1e]. The dehydrating agent is used in an excess amount when a drying agent is used, and when an acid is used as a dehydrating agent, it is used in a catalytic amount.

[0352] The subsequent reduction is carried out by various reduction reactions, for example, by catalytic hydrogenation in the presence of a catalyst in an appropriate solvent. The solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. diethylene glycol dimethyl ether, dioxane, tetrahydrofuran, diethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. dimethylformamide, etc.), or a mixture of these solvents. The catalyst is, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is usually used in an amount of 0.02 to 1 mole to 1 mole of the starting compound. The reaction is usually carried out at a temperature from 20° C. to about 100° C., preferably at a temperature from 0° C. to about 70° C., under a pressure of 1 atm to 10 atms of hydrogen, for 0.5 hour to about 20 hours.

[0353] The above mentioned conditions for the reduction can be employed in the present reduction, but the reduction using a hydrogenating agent is more preferable. The hydrogenating agent includes, for example, lithium aluminum hydride, sodium borohydride, sodium cyanoborohydride, diboran, etc., and is used at least in an amount of 0.1 mole, preferably in an amount of 0.1 mole to 10 moles, to 1 mole of the compound [1e]. The reduction is carried out in an appropriate solvent such as water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, diglyme, etc.), dimethylformamide, or a mixture of these solvents, at a temperature from about −60° C. to about 50° C., preferably at a temperature from −30° C. to room temperature, for about 10 minutes to about 5 hours. When lithium aluminum hydride or diboran is used as a reducing agent, an anhydrous solvent such as diethyl ether, tetrahydrofuran, diglyme, etc., is preferably used.

[0354] wherein R¹, R and X¹ are the same as defined above, R^(5a) is a lower alkyl group having optionally a hydroxy substituent, R¹⁶ and R¹⁷ are each a hydrogen atom or a lower alkyl group, R^(5b) is a benzoyl group having optionally a halogen substituent on the phenyl ring, G_(d) is a group of the formula:

[0355] or a group of the formula:

[0356] G_(e) is a group of the formula:

[0357] or a group of the formula:

[0358] G_(f) is a group of the formula:

[0359] or a group of the formula:

[0360] R^(3a) is a hydrogen atom or a hydroxy-substituted lower alkyl group, and X, Y, R⁴, R^(5a) and R^(5b) are the same as defined above.

[0361] The reaction of the compound [1h] and the compound [10] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6] in above Reaction Scheme-2.

[0362] The reaction of the compound (1h] and the compound [11] is carried out in the presence of a reducing agent in an appropriate solvent or without a solvent. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), acetonitrile, formic acid, acetic acid, ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture thereof. The reducing agent includes, for example, formic acid, ammonium formate, alkali metal salts of fatty acids (e.g. sodium formate, etc.), hydrogenating agents (e.g. sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, etc.), catalysts (e.g. palladium-black, palladium-carbon, platinum oxide, platinum-black, Raney nickel, etc.), and the like.

[0363] When formic acid is used as a reducing agent, the reaction is usually carried out at a temperature from room temperature to about 200° C., preferably at a temperature from about 50° C. to about 150° C., for about one to about 10 hours. Formic acid is used in an excess amount to the compound [1h].

[0364] When a hydrogenating agent is used, the reaction is usually carried out at a temperature from about −30° C. to about 100° C., preferably at a temperature from about 0° C. to about 70° C., for about 30 minutes to about 12 hours. The hydrogenating agent is used in an amount of 1 mole to 20 moles, preferably in an amount of 1 mole to 6 moles, to 1 mole of the compound [1h]. Especially, when lithium aluminum hydride is used as a reducing agent, the solvent is preferably ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, diglyme, etc.) or aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.).

[0365] Moreover, when a catalyst is used, the reaction is usually carried out under atmospheric pressure to 20 atms of hydrogen, preferably, under atmospheric pressure to 10 atms of hydrogen, or in the presence of a hydrogen donor such as formic acid, ammonium formate, cyclohexene, hydrazine hydrate, etc., at a temperature from −30° C. to 100° C., preferably at a temperature from 0° C. to 60° C., for about one to 12 hours. The catalyst is usually used in an amount of 0.1 to 40% by weight, preferably in an amount of 1 to 20% by weight to the amount of the compound [1h]. The hydrogen donor is usually used in an excess amount to the compound [1h].

[0366] The compound [11] is usually used at least in an equimolar amount, preferably in an amount of 1 mole to excess amount, to 1 mole of the compound [1h].

[0367] The reaction of the compound [11] and the compound [12] is carried out under the same conditions as those of the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.

[0368] wherein R¹, R and X¹ are the same as defined above, R¹⁸ is an amino-substituted lower alkanoyl group having optionally a lower alkyl substituent, a lower alkyl group, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: —ACONR⁶R⁷ (A, R⁶ and R⁷ are the same as defined above), G_(g) is a group of the formula:

[0369] or a group of the formula:

[0370] G_(h) is a group of the formula:

[0371] or a group of the formula:

[0372] X, Y and R^(3a) are the same as defined above, R^(18′) is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent, a lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group or a group of the formula: —O—ACONR⁶R⁷ (A, R⁶ and R⁷ are the same as defined above).

[0373] The reaction of the compound [1k] and the compound [13] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0374] wherein R¹, R, X¹ and G^(a) are the same as defined above, G_(i) is a group of the formula:

[0375] or a group of the formula:

[0376] X and Y are the same as defined above, R¹⁹ is a lower alkoxy group, R²⁰ is a hydrogen atom, a lower alkoxycarbonyl group, a lower alkoxy group or a phenyl group, D is a lower alkylene group, n is 0 or 1, and R²¹ is a phenyl group.

[0377] The reaction of the compound [1e] and the compound [14] or the compound [15] is carried out in the presence of a basic compound in an appropriate solvent. The basic compound includes, for example, inorganic bases (e.g. sodium, potassium, sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, etc.), organic bases such as alkali metal alcoholates (e.g. sodium methylate, sodium ethylate, potassium t-butoxide, etc.), an alkyl lithium, aryl lithium or lithium amide (e.g. methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropyl amide, etc.), pyridine, piperidine, quinoline, triethylamine, N,N-dimethylaniline, and the like. The solvent may be any solvent which does not affect the reaction, for example, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), amines (e.g. pyridine, N,N-dimethylaniline, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), and the like. The reaction is usually carried out at a temperature from −80° C. to 150° C., preferably at a temperature from −80° C. to about 120° C., for 0.5 to about 15 hours.

[0378] wherein R¹ and R are the same as defined above, G_(j) is a group of the formula:

[0379] or a group of the formula:

[0380] G_(k) is a group of the formula:

[0381] or a group of the formula:

[0382] G_(l) is a group of the formula:

[0383] or a group of the formula:

[0384] X, Y and D are the same as defined above, and R^(20a) is a lower alkoxycarbonyl group.

[0385] The reaction of converting the compound [1n] into the compound [1o] is carried out under the same conditions as those in the reduction reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. When a hydrogenating agent is used in said reduction reaction, there may preferably be added a metal halide such as a nickel chloride into the reaction system.

[0386] The compound [1n] may be also converted into the compound [1o] by reducing the compound [1n] with metal magnesium-methanol. The reaction is usually carried out at a temperature from 0° C. to 50° C., preferably at a temperature from 0° C. to room temperature, for one to about 10 hours. Metal magnesium is usually used in an amount of 1 to 10 moles, preferably in an amount of 1 to 7 moles, to 1 mole of the compound [1n]. When the compound [1n] wherein X is a methylene group is used in this reaction, there may be obtained the compound [1o] wherein X is a methylene group and the compound [1o] wherein X is a group of the formula: ═CH—, but these compounds [1o] are easily separated.

[0387] The reaction of converting the compound [1o] into the compound [1p] is carried out in the presence or absence of an acid or a basic compound in an appropriate solvent or without a solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) and organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.). The basic compounds includes, for example, metal carbonates (e.g. sodium carbonate, potassium carbonate, etc.), metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, etc.), and the like. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from room temperature to 150° C., for 10 minutes to about 25 hours.

[0388] The compound [1p] is also prepared by treating the compound [1o] in an appropriate solvent in the presence of a dialkyl sulfide-Lewis acid such as dimethyl sulfide-aluminum chloride. The solvent may be the same solvents for the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2. The reaction is usually carried out at a temperature from 0° C. to 70° C., preferably at a temperature from 0° C. to 50° C., for one to 10 hours.

[0389] wherein R¹ and R are the same as defined above, G_(m) is a group of the formula:

[0390] or a group of the formula:

[0391] G_(n) is a group of the formula:

[0392] or a group of the formula:

[0393] R²² is a carboxy-substituted lower alkyl group, and R^(3a), R⁶, R⁷, A, X and Y are the same as defined above.

[0394] The reaction of the compound [1q] and the compound [16] is carried out under the same conditions as those in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.

[0395] wherein G, p, R¹, R⁸, X¹, A, m and R¹³ are the same as defined above, R^(9a) is a benzoyl group having optionally a lower alkyl substituent on the phenyl ring, a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring or a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and R^(12a) is a lower alkanoyl group.

[0396] The reaction of converting the compound [1s] into the compound [1t] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1f] in above Reaction Scheme-3.

[0397] The reaction of the compound [1t] and the compound [17] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0398] The reaction of the compound [1t] and the compound [18] is carried out in the presence or absence of a basic compound in an appropriate solvent or without a solvent. The solvent includes, for example, the above-mentioned aromatic hydrocarbons, lower alcohols (e.g. methanol, ethanol, propanol, etc.), dimethyl formamide, dimethyl sulfoxide, halogenated hydrocarbons (e.g. chloroform, methylene chloride, etc.), acetone, pyridine, and the like. The basic compound includes, for example, organic bases (e.g. triethylamine, pyridine, etc.), sodium hydroxide, potassium hydroxide, sodium hydride, and the like. The reaction is also carried out in the presence of a mineral acid (e.g. sulfuric acid, etc.) in a solvent such as acetic acid.

[0399] The compound [18] is used in an amount of 1 mole to excess amount, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from 0° C. to about 200° C., preferably at a temperature from 0° C. to about 150° C., for 0.5 hour to about 20 hours.

[0400] The starting compound [2a] can be prepared by the processes as illustrated by the following Reaction Scheme.

[0401] wherein G, p, R¹ and R⁸ are the same as defined above.

[0402] The reaction of the compound [2] and the compound [19] is carried out under the same conditions as those in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.

[0403] The reaction of converting the compound [20] into the compound [4] is carried out by (i) subjecting the compound [20] to reduction reaction by using a catalyst in an appropriate solvent, or (ii) subjecting the compound [20] to reduction reaction by using a mixture of a metal or a metal salt with an acid, a metal or a metal salt with an alkali metal hydroxide, a sulfide, an ammonium salt in an appropriate inert solvent.

[0404] When (i) a catalyst is used, the solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, etc.), or a mixture of these solvents. The catalyst includes, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is used in an amount of 0.02 to 1 mole, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from −20° C. to 150° C., preferably at a temperature from 0° C. to about 100° C., under a pressure of 1 to 10 atms of hydrogen, for 0.5 hour to 10 hours. There may be added an acid such as hydrochloric acid into the reaction system.

[0405] When the method (ii) is employed, there is used as a reducing agent a mixture of iron, zinc, tin or stannous chloride and a mineral acid (e.g. hydrochloric acid, sulfuric acid, etc.), or a mixture of iron, iron sulfide, zinc or tin and an alkali metal hydroxide (e.g. sodium hydroxide, etc.), a sulfide (e.g. ammonium sulfide, etc.), aqueous ammonia, an ammonium salt (e.g. ammonium chloride, etc.). The inert solvent includes, for example, water, acetic acid, methanol, ethanol, dioxane, and the like. The conditions for the above reduction can be selected according to the kinds of the reducing agent to be used. For example, when a mixture of stannous chloride and hydrochloric acid is used as a reducing agent, the reaction is preferably carried out at a temperature from 0° C. to about 80° C., for 0.5 hour to about 10 hours. The reducing agent may be used at least in an equimolar amount, usually in an amount of 1 to 5 moles, to 1 mole of the starting compound.

[0406] The starting compound [3] is prepared by the processes as illustrated by the following Reaction Schemes.

[0407] wherein p, R⁸, D and X¹ are the same as defined above, R²⁴ is a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, X² is a halogen atom, R²³ is a lower alkoxycarbonyl group, R²⁵ is a phenoxy group having optionally a lower alkyl substituent on the phenyl ring, R²⁶ is a phenyl group having optionally a lower alkyl substituent on the phenyl ring, R²⁷ is a phenyl-lower alkyl group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent, or a benzoyl-lower alkyl group having optionally a halogen substituent on the phenyl ring.

[0408] The reaction of the compound [21] and the compound [22] and the reaction of the compound [24] and the compound [27] are carried out in the presence of zinc and a catalyst in an appropriate solvent. The solvent includes, for example, ethers (e.g. 1,2-dimethoxyethane, diethyl ether, tetrahydrofuran, dioxane, etc.), acetonitrile, dimethylformamide, and the like. The catalyst includes, for example, palladium compounds or nickel compounds such as tetrakistriphenylphosphine palladium [Pd(PPh₃)₄], palladium acetate [Pd(OCOCH₃)₂], palladium chloride [PdCl₂], bistriphenylphosphinenickel dichloride [Ni(PPh₃)₂Cl₂], and the like. The reaction is usually carried out at a temperature from 0° C. to 70° C., preferably at a temperature from 0° C. to about 50° C., for 1 hour to about 80 hours.

[0409] The compound [24] or the compound [27] is used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [21] or the compound [22], respectively. The catalyst is usually used in an amount of 0.01 to about 1 mole, preferably in an amount of 0.03 to about 0.3 mole, to 1 mole of the starting compound.

[0410] The reaction of the compound [24] and the compound [25] and the reaction of the compound [29] and the compound [30] are carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0411] The reaction of converting the compound [23], [26], [28] or [31] into the compound [3a], [3b], [3c] or [3d], respectively, is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7.

[0412] wherein R²⁸ and R²⁹ are each a lower alkyl group, R³⁰ is a phenyl group having optionally a lower alkyl substituent on the phenyl ring, and p, R⁸ and X² are the same as defined above.

[0413] The reaction of the compound [32] and the compound [33] is carried out in an appropriate solvent. The solvent may be any solvents used in Grignard reaction, but preferably ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, etc.), saturated hydrocarbons (e.g. pentane, hexane, heptane, cyclohexane, etc.), and the like. The compound [33] is usually used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [32]. The reaction is usually carried out at a temperature from −70° C. to 50° C., preferably at a temperature from −30° C. to room temperature, for 1 to about 50 hours.

[0414] The reaction of converting the compound [34] into the compound [35] is carried out in the presence of an oxidizing agent in an appropriate solvent. The oxidizing agent includes, for example, chromic acid pyridinium salts (e.g. pyridinium chlorochromate, pyridinium dichlorochromate, etc.), dimethyl sulfoxide-oxazolyl chloride, dichromic acid, dichromates (e.g. sodium dichromate, potassium dichromate, etc.), permanganic acid, permanganates (e.g. potassium permanganate, sodium permanganate, etc.), manganese dioxide, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and the like. The solvent used in the reaction with an oxidizing agent includes, for example, water, organic acids (e.g. formic acid, acetic acid, trifluoroacetic acid, etc.), alcohols (e.g. methanol, ethanol, etc.), halogenated hydrocarbons (e.g. chloroform, dichloromethane, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, dioxane, etc.), dimethylsulfoxide, dimethylformamide, or a mixture of these solvents. The oxidizing agent is usually used at least in an equimolar amount, preferably in an amount of 1 mole to 25 moles, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from about 0° C. to about 100° C., preferably at a temperature from 0° C. to about 70° C., for 1 hour to about 7 hours.

[0415] The reaction of converting the compound [35] into the compound [3e] is carried out by subjecting the compound [35] to alkylation in the presence of an alkylating agent in an appropriate solvent, followed by subjecting the product to hydrolysis, or by subjecting directly the compound [35] to hydrolysis.

[0416] In the alkylation of the compound [35], the alkylating agent used therein includes, for example, an alkyl halide such as methyl iodide, etc. The alkylation reaction is usually carried out at a temperature from room temperature to about 200° C., preferably at a temperature from room temperature to about 150° C., for 1 hour to about 30 hours. The solvent includes, for example, ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethyl ether, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), polar solvents (e.g. dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, acetone, acetonitrile, nitromethane, etc.), and the like. The alkylating agent is usually used in an equimolar amount, preferably in an amount of 1 to 8 moles, to 1 mole of the compound [35].

[0417] The subsequent hydrolysis may be carried out by a conventional method, for example, by in the presence of a basic compound (e.g. sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, barium hydroxide, etc.), or a mineral acid (e.g. hydrochloric acid, sulfuric acid, etc.), or an organic acid (e.g. acetic acid, etc.), in a solvent such as water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, ethylene glycol dimethyl ether, etc.), acetic acid, or a mixture of these solvents. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from room temperature to 150° C., for 0.5 hour to 20 hours.

[0418] In the reaction of subjecting directly the compound [35] to hydrolysis, the reaction is carried out under the same conditions as those in the above hydrolysis. The reaction is carried out for 1 hour to 30 hours.

[0419] The compound [3e] is also prepared by subjecting the compound [35] to hydrolysis in the presence of a mineral acid (e.g. sulfuric acid, hydrochloric acid, nitric acid, etc.), or in the presence of an organic acid (e.g. acetic acid, aromatic sulfonic acid, etc.) under the same conditions such as solvents, reaction temperature, reaction period, as those in the above hydrolysis reaction.

[0420] The starting compound [32] is prepared by the processes as illustrated in the following Reaction Scheme.

[0421] wherein p, R⁸, X², R²⁸, R²⁹ and X² are the same as defined above.

[0422] The reaction of the compound [36] and the compound [37] is carried out under the same conditions as those in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1 wherein a carboxylic acid halide is used. The compound [37] is used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [36].

[0423] The reaction of the compound [38] and the compound [39] is carried out in a solvent such as ethers (e.g. diethyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), aliphatic hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), at a temperature from 0° C. to 150° C., preferably at a temperature from 0° C. to about 100° C., for 0.5 hour to about 5 hours. The compound [39] is used at least in an equimolar amount, preferably in an amount of 1 to 1.5 mole, to 1 mole of the compound [38].

[0424] wherein p, R⁸, R²³, R²¹ and X¹ are the same as defined above, and R³¹ is a phenyl group having optionally a halogen substituent.

[0425] The reaction of the compound [39A] and the compound [40] is carried out under the same conditions as those in the reaction of the compound [1e] and the compound [14] or the compound [15] in above Reaction Scheme-6.

[0426] The reaction of converting the compound [41] into the compound [3f] is carried out under the same conditions as those in the reaction of converting the compound [10] into the compound [1p] in above Reaction Scheme-6.

[0427] wherein p, R⁸ and R²³ are the same as defined above, R³² is a lower alkylsulfonyloxy group having optionally a halogen substituent, or a halogen atom, and R³³ is a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a phenyl group and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent.

[0428] The reaction of the compound [42] and the compound [43] is carried out in an appropriate solvent in the presence or absence of a lithium compound such as lithium chloride, etc., in the presence of a basic compound and a catalyst. The solvent may be the same solvents as those used in the reaction of the compound [38] and the compound [39] in above Reaction Scheme-13. The basic compound may be the same basic compounds as those used in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1 wherein a carboxylic acid halide is used. The catalyst includes, for example, tetrakis(triphenylphosphine)palladium, palladium chloride, and the like. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from room temperature to about 150° C., for one to about 10 hours. The basic compound and the lithium compound are each used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [42]. The catalyst is used in a catalytic amount.

[0429] The reaction of converting the compound [44] into the compound [3g] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7.

[0430] wherein G, p, R¹, R⁸ and R^(10a) are the same as defined above, R^(11c) is a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a benzoyl-lower alkyl group, or a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, R^(11d) is in addition to the groups for R^(11c), a phenyl group having optionally a substituent selected from a lower alkyl group and a halogen atom.

[0431] The reaction of the compound [4] and the compound [45] is carried out in the presence of a dialkyl azodicarboxylate (e.g. diethyl azodicarboxylate, dibutyl diazodicarboxylate, etc.), a dialkyl azodicarboxyamide (e.g. 1,1′-azodicarbonyldi(piperidine), etc.), and a phosphorus compound (e.g. a trialkylphosphine, a triarylphosphine, etc.). The solvent includes, for example, ethers (e.g. tetrahydrofuran, 1,2-dimethoxyethane, diethyl ether, diisopropyl ether, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, etc.), or a mixture of these solvents. The dialkyl azodicarboxylate, the phosphorus compound and the compound [45] are each used at least in an equimolar amount, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from −20° C. to 100° C., preferably at a temperature from −20° C. to 50° C., for 1 hour to 30 hours.

[0432] The compound [1v] wherein R^(10a) is a lower alkanoyl group having optionally a halogen substituent may be converted into the corresponding compound [1w] by subjecting the compound [1v] to hydrolysis. The hydrolysis is carried out under the same conditions as those in the hydrolysis of the compound [1] wherein R⁹ is a phenyl group having at least one lower alkanoyloxy substituent on the phenyl ring.

[0433] The reaction of the compound [4] and the compound [46] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. The compound [46] is used at least in an equimolar amount, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4].

[0434] wherein G, p, R¹, R⁸, X¹ and X² are the same as defined above.

[0435] The reaction of the compound [4a] and the compound [47] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0436] wherein G, p, R¹, R⁸ and X¹ are the same as defined above, and R³⁴ is a lower alkyl group, a lower alkanoyl group, a phenyl-lower alkyl group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, or a pyrrolidinyl-substituted lower alkyl group.

[0437] The reaction of the compound [48] and the compound [49] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0438] wherein G, p, R¹ and R⁸ are the same as defined above, and R³⁵ is an anilino group having optionally a lower alkyl substituent on the phenyl ring.

[0439] The reaction of the compound [1A] and the compound [50] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. The compound [50] is used at least in an equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the compound [1A].

[0440] wherein R³⁶ is a lower alkoxy group or a halogen atom, R³⁷ is a lower alkyl group, R⁸, R²⁸, R²⁹, R⁹ and X² are the same as defined above, and q is 0 or 1.

[0441] The reaction of the compound [51] and the compound [52] is carried out under the same conditions as those in the reaction of the compound [32] and the compound [33] in above Reaction Scheme-12. The compound [52] is used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [51].

[0442] wherein R⁸, p, R³² and R²³ are the same as defined above, R³⁸ is a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, or an amino-substituted lower alkoxy group having optionally a lower alkyl substituent, and r is 0, 1 or 2.

[0443] The reaction of the compound [54] and the compound [55] is carried out under the same conditions as those in the reaction of the compound [42] and the compound [43] in above Reaction Scheme-15.

[0444] The reaction of converting the compound [56] into the compound [3i] is carried out under the same conditions as those in the reaction of converting the compound [44] into the compound [3g] in above Reaction Scheme-15.

[0445] wherein R²⁸, R²⁹, R⁸, p, X¹ and X² are the same as defined above, s is an integer of 0 to 5, and R^(39′) is a lower alkyl group.

[0446] The reaction of the compound [32] and the compound [57] is carried out under the same conditions as those in the reaction of the compound [32] and the compound [33] in above Reaction Scheme-12.

[0447] The reaction of the compound [58] and the compound [59] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0448] The reaction of the compound [38] and the compound [57] is carried out under the same conditions as those in the reaction of the compound [1e] and the compound [14] or the compound [15] in above Reaction Scheme-6. The compound [57] is used at least in an equimolar amount, preferably in an amount of 1 to 1.5 mole, to 1 mole of the compound [38].

[0449] The reaction of converting the compound [58] or the compound [60] into the compound [3j] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7, except the reaction is carried out for 1 hour to about 50 hours.

[0450] The reaction of converting the compound [3j] into the compound [3k] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3.

[0451] wherein R⁸, p and X² are the same as defined above, R⁴⁹ is a cyano group, a lower alkoxycarbonyl group or a carboxy group, R³⁹ is a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl lower alkyl group, or an oxo group, and t is an integer of 0 to 3, and the group of the formula:

[0452] is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom.

[0453] The reaction of the compound [61] and the compound [62] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0454] When the compound [63] is a compound of the formula [63] wherein R⁴⁹ is a cyano group or a lower alkoxycarbonyl group, the reaction of converting the compound [63] into the compound [3k] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7.

[0455] wherein G, R¹, R⁸, p and R^(10a) are the same as defined above, R^(11e) is a lower alkanoyl group having a halogen substituent, R⁴⁰ is a phenyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a lower alkanoyl-substituted amino group, a nitro group and a halogen atom, a lower alkyl group, a lower alkanoyl group, a quinolyl group, a tetrahydroquinolyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, or a tetrahydronaphthyl group, R^(11f) is a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a lower alkanoyl-substituted amino group, a nitro group and a halogen atom on the phenyl ring, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a quinolyloxy-substituted lower alkanoyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, or a tetrahydronaphthyloxy-substituted lower alkanoyl group.

[0456] The reaction of the compound [1C] and the compound [63] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0457] The compound [1D] wherein R^(11f) is a lower alkanoyloxy-substituted lower alkanoyl group is reacted under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7 to give the compound [1D] wherein the corresponding R^(11f) is a lower alkanoyl group having a hydroxy substituent.

[0458] wherein R¹, G, R⁸, p and R^(10a) are the same as defined above, and R⁴⁹ is a tetrahydroisoquinolyl group or a group of the formula:

[0459] The reaction of converting the compound [4] into the compound [1E] is carried out by (i) reacting the compound [4] with a carbonylating agent in the presence of a basic compound in an appropriate solvent, followed by (ii) reacting the resulting product with the compound [65] in the presence of a basic compound in an appropriate solvent.

[0460] The solvent and the basic compound used in the above process (i) may be each the same ones as those used in the reaction of reacting a carboxylic acid halide with the amine compound [2] in above Reaction Scheme-1. The carbonylating agent includes, for example, carbonyldiimidazole, phosgene, diphosgene, urea, triphosgene, etc. The carbonylating agent is usually used in an amount of 0.05 to 1 mole, preferably in an amount of 0.1 to 1 mole, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from 0° C. to 200° C., preferably at a temperature from 0° C. to about 180° C., for 1 hour to about 10 hours.

[0461] The solvent and the basic compound used in the above process (ii) may be each the same ones as those used in the process (i). The processes (i) and (ii) are carried out in one-pot system. The compound [65] is used in an amount of 1 to 5 moles, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from room temperature to 150° C., preferably at a temperature from room temperature to about 120° C., for 0.5 hour to about 5 hours.

[0462] wherein R¹, R², R³, R and X¹ are the same as defined above, and R^(A′) is the same groups as those for R^(A) other than a hydrogen atom.

[0463] The reaction of the compound [1F] and the compound [66] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0464] wherein R¹, G, R⁸, p and X¹ are the same as defined above.

[0465] The reaction of converting the compound [1H] into the compound [1I] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0466] wherein R¹, G, R⁸, p and R^(10a) are the same as defined above, R⁴⁴ is a lower alkyl group having optionally a halogen substituent, a phenoxy-lower alkyl group, a phenyl-lower alkyl group, a pyridyl-lower alkyl group, a fluorenyl-lower alkyl group, a lower alkenyl group or a piperidinyl-lower alkyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring.

[0467] The reaction of converting the compound [4] into the compound [67] is carried out under the same conditions as those in the reaction of converting the compound [4] into the compound [1E] in above Reaction Scheme-25.

[0468] wherein R¹ and R are the same as defined above, G_(o) is a group of the formula:

[0469] or a group of the formula:

[0470] G_(p) is a group of the formula:

[0471] or a group of the formula:

[0472] R^(3a), X and Y are the same as defined above, R⁴⁵ is a cyano-substituted lower alkyl group, R⁴⁶ is a tetrazolyl-substituted lower alkyl group, and M is an alkali metal such as sodium, potassium, etc.

[0473] The reaction of converting the compound [1K] into the compound [1L] is carried out by reacting the compound [1K] with the compound [68] in the presence of a basic compound in an appropriate solvent. The solvent includes, for example, halogenated hydrocarbons (e.g. chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. dioxane, diethylene glycol dimethyl ether, diethyl ether, tetrahydrofuran, etc.), polar solvents (e.g. dimethylformamide, dimethylacetamide, N-methylpyrrolidone, acetic anhydride, acetonitrile, dimethyl sulfoxide, hexamethylphosphoric triamide, etc.). The basic compound includes, for example, inorganic bases (e.g. sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium hydride, sodium, potassium, sodium amide, etc.), or organic bases (e.g. N,N-dimethylaniline, piperidine, pyridine, triethylamine, sodium acetate, potassium acetate, etc.). The compound [68] is used at least in an equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the compound [1K]. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from 50° C. to about 150° C., for 1 hour to about 40 hours.

[0474] wherein R⁸, p, R⁹ and R²³ are the same as defined above, R⁴⁷ is a lower alkylsulfonyloxy group having optionally a halogen substituent, and R⁴⁸ is a lower alkyl group.

[0475] The reaction of the compound [69], carbon monooxide [70] and the compound [71] is carried out in the presence of a catalyst and a basic compound in an appropriate solvent. The solvent and the basic compound used therein are the same ones as those used in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1 wherein a carboxylic acid halide is used. The catalyst includes, for example, palladium acetate, 1,3-bis(diphenylphosphino)propane (dppp), and the like. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from room temperature to about 150° C., for 1 hour to about 10 hours. The compound [70], the compound [71] and the catalyst are each used in an excess amount to the compound [69].

[0476] wherein R⁵⁰ is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group, and R³², R²³, R⁸, p, X¹ and X² are the same as defined above.

[0477] The reaction of the compound [72] and the compound [73] is carried out under the same conditions as in the reaction of the compound [54] and the compound [55] in above Reaction Scheme-21.

[0478] The reaction of converting the compound [74] into the compound [3m] is carried out under the same conditions as in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7.

[0479] The reaction of the compound [72] and the compound [75] is carried out under the same conditions as in the reaction of the compound [54] and the compound [55] in above Reaction Scheme-21.

[0480] The reaction of converting the compound [76] into the compound [3m] is carried out in the presence of a basic compound and an oxidizing agent in an appropriate solvent. The solvent and the oxidizing agent used therein are the same ones as those used in the reaction of converting the compound [34] into the compound [35] in above Reaction Scheme-12.

[0481] The basic compound includes, for example, sodium hydroxide, potassium hydroxide, sodium hydride, etc.

[0482] The oxidizing agent is used at least in an equimolar amount, preferably in an amount of 1 to 4 moles, to 1 mole of the compound [76].

[0483] The reaction is usually carried out at a temperature from 0° C. to about 150° C., preferably at a temperature from 0° C. to about 120° C., for about 1 hour to about 7 hours.

[0484] The reaction of the compound [77] and the compound [78] is carried out by treating the compound [77] with a basic compound in an appropriate solvent, at a temperature from −80° C. to 50° C., preferably at a temperature from −80° C. to room temperature, for 0.5 hour to 5 hours, and followed by reacting the product with the compound [78] in the presence of a zinc compound (e.g. zinc, zinc chloride, etc.), a catalyst and a basic compound in the same solvent.

[0485] The basic compound used for the treatment of the compound [77] includes an alkyl lithium, an aryl lithium, or a lithium amide, for example, methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropylamide, and the like. The basic compound is used at least in an quimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [77]. The solvent and the catalyst are the same as those in the reaction of the compound [21] and the compound [22] in above Reaction Scheme-11, and are used in the same amount as those in said reaction in above Reaction Scheme-11.

[0486] The reaction of the product derived from the compound [77] and the compound [78] is usually carried out at a temperature from 0° C. to 150° C., preferably at a temperature from 0° C. to 10° C., for 1 hour to about 10 hours.

[0487] The basic compound used in the reaction of the product derived from the compound [77] and the compound [78] includes, for example, in addition to diisopropylethylamine, the same basic compounds used in the reaction of a carboxylic acid halide of the compound [3] and the amine compound [2] in above Reaction Scheme-1.

[0488] The zinc compound and the basic compound used in the reaction of the product derived from the compound [77] and the compound [78] are used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [77].

[0489] The reaction of converting the compound [79] into the compound [74] is carried out by subjecting the compound [79] to catalytic hydrogenation in an appropriate solvent. The solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethyl formamide, etc.), or a mixture of these solvents. The catalyst includes, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is usually used in an amount of 0.02 to 1 mole, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from −20° C. to about 150° C., preferably at a temperature from 0° C. to about 100° C., under 1 to 10 atms of hydrogen, for 0.5 hour to about 10 hours.

[0490] There may be added sodium acetate, etc. into the reaction system.

[0491] wherein R¹, G, R⁸, p, X¹, R³⁹ and t are the same as defined above.

[0492] The reaction of the compound [80] and the compound [81] is carried our under the same conditions as in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0493] wherein R¹, G, R⁸ and p are the same as defined above, and R⁵¹ and R⁵² are each a lower alkyl group.

[0494] The reaction of the compound [4a] and the compound [82] is carried out in the presence of an acid in an appropriate solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.).

[0495] The reaction is usually carried out at a temperature from room temperature to about 200° C., preferably at a temperature from room temperature to about 150° C., for 0.5 hour to about 5 hours. The compound [82] is used at least in an equimolar amount, preferably in an mount of 1 to 2 moles, to 1 mole of the compound [4a].

[0496] The compound of the formula [1] wherein R¹ is a hydroxy group can be prepared by subjecting the compound of the formula [1] wherein R¹ is a lower alkoxy group to de-alkylation. The de-alkylation reaction is carried out in the presence of an acid in an appropriate solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), polar solvents (e.g. acetonitrile, etc.), organic acids (e.g. acetic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), Lewis acids (e.g. boron trifluoride, aluminum chloride, boron tribromide, etc.), iodides (e.g. sodium iodide, potassium iodide, etc.), and a mixture of a Lewis acid and a iodide. The reaction is usually carried out at a temperature from room temperature to 150° C., preferably at a temperature from room temperature to 120° C., for 0.5 hour to 15 hours.

[0497] The compound of the formula [1] wherein R⁹ is a phenyl group having at least one phenyl-lower alkoxy substituent on the phenyl ring is converted into the compound of the formula [1] wherein R⁹ is a phenyl group having at least one hydroxy substituent on the phenyl ring by subjecting it to catalytic reduction. The catalytic reduction is carried out in the presence of a reducing agent in an appropriate solvent. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), acetic acid, ethyl acetate, ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture of these solvents. The reducing agent includes, for example, catalysts such as palladium-black, palladium-carbon, platinum oxide, platinum-black, platinum-carbon Raney nickel, etc. The reaction is usually carried out at a temperature from −30° to 100° C., preferably at a temperature from 0° C. to 60° C., under a pressure from atmospheric pressure to 10 atms of hydrogen. The catalyst is usually used in an amount of 0.1 to 40% by weight, preferably in an amount of 0.1 to 20% by weight, to the amount of the starting compound.

[0498] The compound of formula [1] wherein R⁹ is a phenyl group having at least one lower alkanoyloxy substituent on the phenyl ring, or a lower alkanoyloxy group can be converted into the compound of the formula [1] wherein R⁹ is a phenyl group having at least one hydroxy substituent on the phenyl ring or a hydroxy group, respectively, by subjecting them to hydrolysis. The hydrolysis is carried out in the presence of an acid or a basic compound in an appropriate solvent or without a solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether etc.), fatty acids (e.g. formic acid, acetic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acids, etc.), and the like. The basic compound includes, for example, metal carbonates (e.g. sodium carbonate, potassium carbonate, etc.), metal hydroxides (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), and the like. The reaction is usually carried out at a temperature from room temperature to about 200° C., preferably at a temperature from room temperature to about 150° C., for 0.5 to about 25 hours.

[0499] The compound of the formula [1] wherein R⁸ is a lower alkoxy group can be converted into the compound of the formula [1] wherein R⁸. is a hydroxy group by subjecting it to de-alkylation reaction. The compound [1] wherein R⁹ is a phenyl group having at least one lower alkoxy substituent on the phenyl ring can be converted into the compound of the formula [1] wherein R⁹ is a phenyl group having at least one hydroxy substituent on the phenyl ring by subjecting it to de-alkylation reaction. The de-alkylation reaction is carried out in the presence of an acid in an appropriate solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), polar solvents (e.g. acetonitrile, etc.), organic acids (e.g. acetic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), Lewis acids (e.g. boron trifluoride, aluminum chloride, boron tribromide, etc.), iodides (e.g. sodium iodide, potassium iodide, etc.), and a mixture of a Lewis acid and a iodide. The reaction is usually carried out at a temperature from room temperature to 150° C., preferably at a temperature from room temperature to 120° C., for 0.5 hour to about 15 hours.

[0500] The compound of the formula [1] wherein R¹¹ is a phenoxy-lower alkanoyl group having at least one amino substituent on the phenyl ring can be converted into the compound of the formula [1] wherein R¹¹ is a phenoxy-lower alkanoyl group having at least one amino substituent having a lower alkyl substituent on the phenyl ring by reacting it with a compound of the formula: R⁴¹X¹ [10a] (wherein R⁴¹ is a lower alkyl group and X¹ is the same as defined above), or a compound of the formula: R¹⁶COR¹⁷ [11] (wherein R¹⁶ and R¹⁷ are the same as defined above) under the same conditions as those in the reaction of the compound [1h] and the compound [10] or the compound [11] in above Reaction Scheme-4.

[0501] The compound of the formula [1] wherein R⁹ is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom wherein these heteroatoms may optionally be substituent, and said heterocyclic group has a secondary amino group on the heterocyclic nucleus, is reacted with a compound of the formula: R⁴²X [10b] (wherein X is the same as defined above and R⁴² is a lower alkyl group, a phenyl-lower alkyl group or a lower alkanoyl group) or a group of the formula: R¹⁶COR¹⁷ [11] (wherein R¹⁶ and R¹⁷ are the same as defined above) under the same conditions as those in the reaction of the compound [1h] with the compound [10] or the compound [11] in above Reaction Scheme-4, to give the compound of the formula [1] wherein the corresponding R⁹ is the above heterocyclic group wherein the secondary amino group on the heterocyclic nucleus is substituted by a lower alkyl group, a phenyl-lower alkyl group or a lower alkanoyl group, or reacted with a compound of the formula: R⁴³OH [12a] (wherein R⁴³ is a lower alkanoyl group) under the same conditions as those in the reaction of the compound [2] with the compound [3] in above Reaction Scheme-1 to give the compound of the formula [1] wherein the corresponding R⁹ is a heterocyclic group wherein the secondary amino group on the heterocyclic nucleus is substituted by a lower alkanoyl group.

[0502] Among the desired compounds [1] of the present invention, the compounds having an acidic group can easily be converted into salts by treating with a pharmaceutically acceptable basic compound. The basic compound includes, for example, metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, etc.), alkali metal carbonates or hydrogen carbonates (e.g. sodium carbonate, sodium hydrogen carbonate, etc.) and alkali metal alcoholates (e.g. sodium methylate, potassium ethylate, etc.). Besides, among the desired compounds [1] of the present invention, the compounds having a basic group can easily be converted into acid addition salts thereof by treating with a pharmaceutically acceptable acid. The acid includes, for example, inorganic acids (e.g. sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, etc.), and organic acids (e.g. acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, fumaric acid, citric acid, succinic acid, benzoic acid, etc.). These salts show as well excellent pharmacological activities as the desired compounds [1].

[0503] In addition, the compounds [1] of the present invention include stereoisomers and optical isomers, and these isomers are also useful as a vasopressin antagonist, vasopressin agonist or an oxytocin antagonist.

[0504] The compounds of the present invention thus obtained can easily be isolated and purified by conventional isolation methods. The isolation methods are, for example, distillation method, recrystallization method, column chromatography, ion exchange chromatography, gel chromatography, affinity chromatography, preparative thin layer chromatography, extraction with a solvent, and the like.

[0505] The desired compounds [1] of the present invention and salts thereof are useful as a vasopressin antagonist, vasopressin agonistic activities and an oxytocin antagonist, and are used in the form of a conventional pharmaceutical preparation. The preparation is prepared by using conventional diluents or carriers such as fillers, thickening agents, binders, wetting agent, disintegrators, surfactants, lubricants, and the like. The pharmaceutical preparations can be selected from various forms in accordance with the desired utilities, and the representative forms are tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.), and the like. In order to form in tablets, there are used carriers such as vehicles (e.g. lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, etc.), binders (e.g. water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrators (e.g. dry starch, sodium alginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, stearic monoglyceride, starches, lactose, etc.), disintegration inhibitors (e.g. white sugar, stearin, cacao butter, hydrogenated oils, etc.), absorption promoters (e.g. quaternary ammonium base, sodium laurylsulfate, etc.), wetting agents (e.g. glycerin, starches, etc.), adsorbents (e.g. starches, lactose, kaolin, bentonite, colloidal silicates, etc.), lubricants (e.g. purified talc, stearates, boric acid powder, polyethylene glycol, etc.), and the like. Moreover, the tablets may also be in the form of a conventional coated tablet, such as sugar-coated tablets, gelatin-coated tablets, enteric coated tablets, film coating tablets, or double or multiple layer tablets. In the preparation of pills, the carriers include vehicles (e.g. glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin, talc, etc.), binders (e.g. gum arabic powder, tragacanth powder, gelatin, ethanol, etc.), disintegrators (e.g. laminaran, agar, etc.), and the like. In the preparation of suppositories, the carriers include, for example, polyethylene glycol, cacao butter, higher alcohols, higher alcohol esters, gelatin, semi-synthetic glycerides, and the like. Capsules can be prepared by charging a mixture of the compound of the present invention and the above carriers into hard gelatin capsules or soft capsules in usual manner. In the preparation of injections, the solutions, emulsions and suspensions are sterilized and are preferably made isotonic with the blood. In the preparation of these solutions, emulsions and suspensions, there are used conventional diluents, such as water, ethyl alcohol, macrogol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, and the like. In this case, the pharmaceutical preparations may also be incorporated with sodium chloride, glucose, or glycerin in an amount sufficient to make them isotonic, and may also be incorporated with conventional solubilizers, buffers, anesthetizing agents. Besides, the pharmaceutical preparations may optionally be incorporated with coloring agents, preservatives, perfumes, flavors, sweeting agents, and other medicaments, if required.

[0506] The amount of the desired compound of the present invention to be incorporated into the vasopressin antagonist, vasopressin agonist or the oxytocin antagonist is not specified but may be selected from a broad range, but usually, it is preferably in the range of 1 to 70% by weight, more preferably 5 to 50% by weight.

[0507] The vasopressin antagonist, the vasopressin agonist or the oxytocin antagonist containing as an active ingredient the compounds [1] of the present invention or a salt thereof may be administered in any method, and a suitable method for administration may be determined in accordance with various forms of preparations, ages, sexes and other conditions of the patients, the degree of severity of diseases, and the like. For example, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally. The injections are intravenously administered alone or together with a conventional auxiliary liquid (e.g. glucose, amino acid solutions), and further are optionally administered alone in intramuscular, intracutaneous, subcutaneous, or intraperitoneal route, if required. Suppositories are administered in intrarectal route.

[0508] The dosage of the vasopressin antagonist, the vasopressin agonist and the oxytocin antagonist of the present invention may be selected in accordance with the usage, ages, sexes and other conditions of the patients, the degree of severity of the diseases, and the like, but it is usually in the range of about 0.6 to 50 mg of the active compound of the present invention per 1 kg of body weight of the patient per day. The active compound is preferably contained in an amount of about 10 to about 1000 mg per the dosage unit.

[0509] Best Mode for Carrying Out the Invention

EXAMPLES

[0510] The present invention is illustrated in more detail by the following Preparations of vasopressin antagonist, vasopressin agonist or oxytocin antagonist, Reference Examples of processes for preparing the starting compounds to be used for preparing the desired compounds of the present invention, and Examples of processes for preparing the desired compounds, and Experiments of the activities of the desired compounds of the present invention.

[0511] Preparation 1

[0512] Film coated tables are prepared from the following components. Components Amount 7-Chloro-5-[(4-methyl-1-piperazinyl)carbonyl- 150 g  methyl]-1-[2-methoxy-4-(2-methylphenyl)- benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine Avicel (trademark of microcrystalline cellulose 40 g manufactured by Asahi Chemical Industry, Co., Ltd., Japan) Corn Starch 30 g Magnesium stearate  2 g Hydroxypropyl methylcellulose 10 g Polyethylene glycol-6000  3 g Castor oil 40 g Ethanol 40 g

[0513] The active compound of the present invention, Avicel, corn starch and magnesium stearate are mixed and kneaded and the mixture is tabletted by using a conventional pounder (R 10 mm) for sugar coating. The tablets thus obtained are coated with a film coating agent consisting of hydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil and ethanol to give film coated tablets.

[0514] Preparation 2

[0515] Tablets are prepared from the following components. Components Amount 7-Chloro-5-{[N-(2-diethylaminoethyl)-N-methyl- 150 g amino]carbonylmethyl}-1-(3,4-dimethoxybenzoyl)- 2,3,4,5-tetrahydro-1H-benzazepine Citric acid 1.0 g Lactose 33.5 g Dicalcium phosphate 70.0 g Pullonic F-68 30.0 g Sodium laurylsulfate 15.0 g Polyvinylpyrrolidone 15.0 g Polyethylene glycol (Carbowax 1500) 4.5 g Polyethylene glycol (Carbowax 6000) 45.0 g Corn starch 30.0 g Dry sodium stearate 3.0 g Dry magnesium stearate 3.0 g Ethanol q.s.

[0516] The active compound of the present invention, citric acid, lactose, dicalcium phosphate, Pullonic F-68 and sodium laurylsulfate are mixed. The mixture is screened with No. 60 screen and is granulated with an alcohol solution containing polyvinylpyrrolidone, Carbowax 1500 and 6000. If required, an alcohol is added thereto so that the powder mixture is made a paste-like mass. Corn starch is added to the mixture and the mixture is continuously mixed to form uniform particles. The resulting particles are passed through No. 10 screen and entered into a tray and then dried in an oven at 100° C. for 12 to 14 hours. The dried particles are screened with No. 16 screen and thereto are added dry sodium laurylsulfate and dry magnesium stearate, and the mixture is tabletted to form the desired shape.

[0517] The core tablets thus prepared are vanished and dusted with talc in order to guard them from wetting. Undercoating is applied to the core tablets. In order to administer the tablets orally, the core tablets are vanished several times. In order to give round shape and smooth surface to the tablets, further undercoating and coating with a lubricant are applied thereto. The tablets are further coated with a coloring coating materials until the desired colored tablets are obtained. After drying, the coated tablets are polished to obtain the desired tablets having uniform gross.

[0518] Preparation 3

[0519] An injection preparation is prepared from the following components. Components Amount 7-Chloro-5-[(4-methyl-1-piperazinyl)carbonyl- 5 g methyl]-1-[2-methoxy-4-(2,4-dichlorobenzylamino)- benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine Polyethylene glycol (molecular weight; 4000) 0.3 g Sodium chloride 0.9 g Polyoxyethylene-sorbitan monooleate 0.4 g Sodium metabisulfite 0.1 g Methyl-paraben 0.18 g Propyl-paraben 0.02 g Distilled water for injection 10.0 ml

[0520] The above parabens, sodium metabisulfite and sodium chloride are dissolved in distilled water of about half volume of the above with stirring at 80° C. The solution thus obtained is cooled to 40° C., and the active compound of the present invention and further polyethylene glycol and polyoxyethylene sorbitan monooleate are dissolved in the above solution. To the solution is added distilled water for injection to adjust to the desired volume, and the solution is sterilized by filtering with an appropriate filter paper to give an injection preparation.

Reference Example 1

[0521] 4-Chloromethylbenzoic acid methyl ester (26.36 g) is dissolved in 1,2-dimethoxyethane (700 ml), and thereto are added with stirring zinc powder (20.6 g) and bistriphenylphosphine palladium dichloride (5 g) over an ice-bath. To the mixture is added dropwise o-toluoyl chloride (26.5 g), and the mixture is stirred over an ice-bath for three hours, and then stirred at room temperature for three days. The insoluble materials are removed by filtration, and the residue is washed with ethyl acetate. To the mother liquor is added a saturated sodium hydrogen carbonate solution, and the mixture is extracted with ethyl acetate. The organic layer is washed successively with a saturated sodium hydrogen carbonate solution, a 0.5N hydrochloric acid and a saturated sodium chloride solution, dried over magnesium sulfate and concentrated. The residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=50:1˜10:1), and recrystallized from toluene/n-hexane to give 4-[(2-methylbenzoyl)methyl]benzoic acid methyl ester (15 g).

Reference Example 2

[0522] 4-Methoxycarbonylbenzyltriphenylphosphonium chloride (19.1 g) and sodium methylate (2.77 g) are suspended in methanol (20 ml), and the mixture is stirred at room temperature for one hour. To the mixture is added o-chlorobenzaldehyde (5 g), and the mixture is stirred at room temperature for one hour. Sodium methylate (5.54 g) is added to the mixture, and the mixture is stirred at room temperature for one hour. The reaction mixture is concentrated, and to the residue is added water, and the mixture is extracted with ethyl acetate. The organic layer is washed successively with water, a 0.5N hydrochloric acid and a saturated sodium chloride solution, and dried over magnesium sulfate, and concentrated. To the residue is added diethyl ether/n-hexane, and the insoluble materials are removed by filtration. The mother liquor is concentrated, and the residue is purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=30:1). Methyl 4-(2-chlorostyryl)benzoate (cis form) (2.15 g) is firstly eluted, and then, methyl 4-(2-chlorostyryl)benzoate (trans form) (1.42 g) is eluted, and both are collected as white powder.

Reference Example 3

[0523] A mixture of methyl 4-(2-chlorostyryl)benzoate (trans form) (1.42 g), 5N sodium hydroxide (1.6 ml) and methanol (20 ml) is stirred at room temperature for three hours, and refluxed for two hours. The mixture is evaporated to remove the methanol, and to the residue is added water. The mixture is acidified with conc. hydrochloric acid, and stirred at room temperature for 16 hours. The precipitated crystals are collected by filtration to give 4-(2-chlorostyryl)benzoic acid (1.36 g) as white powder.

Reference Example 4

[0524] 4-Bromobenzoic acid (7.2 g) and thionyl chloride (20 ml) are refluxed for one hour, and concentrated. To the residue is added toluene, and the mixture is concentrated. The obtained 4-bromobenzoic chloride is added dropwise to a mixture of 2-amino-2-methyl-1-propanol (5.1 ml), triethylamine (10 ml) and dichloromethane (70 ml) under ice-cooling. The reaction mixture is stirred at room temperature for five hours, and thereto is added ice, and the mixture is extracted with dichloromethane. The organic layer is washed successively with 0.5N hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and a saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is dissolved in dichloromethane (50 ml), and thereto is added dropwise thionyl chloride (7.8 ml) under ice-cooling. The mixture is stirred at room temperature for three hours, cooled with ice, and basified with a 5N aqueous sodium hydroxide solution. The mixture is extracted with dichloromethane, and the organic layer is washed with water, dried over magnesium sulfate to give 2-(4-bromophenyl)-4,4-dimethyl-2-oxazoline (8.35 g) as colorless oil.

Reference Example 5

[0525] To a solution of 2-(4-bromophenyl)-4,4-dimethyl-2-oxazoline (1 g) in dry tetrahydrofuran (10 ml) are added dropwise magnesium (526 mg) and dry tetrahydrofuran (50 ml) under refluxing. The heating of the mixture is stopped, and thereto is added 2-(4-bromphenyl)-4,4-dimethyl-2-oxazoline (4 g) at a slowly refluxing rate, during which the mixture is stirred for 30 minutes, and then thereto is added o-tolualdehyde (2.16 ml) under ice-cooling. The mixture is stirred under ice-cooling for one hour, and stirred at room temperature for two hours, and the reaction is quenched with adding thereto a saturated aqueous ammonium chloride solution. The mixture is extracted with ethyl acetate, and the organic layer is washed successively with 1N hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and a saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=4˜2:1) to give 2-{4-[1-(2-methylphenyl)-1-hydroxymethyl]phenyl}-4,4-dimethyl-2-oxazoline (3.07 g) as white powder.

[0526]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35 (6H, s), 2.24 (3H, s), 3.04 (1H, d, J=4 Hz), 4.08 (1H, s), 5.99 (1H, d, J=4 Hz), 7.03-7.05 (6H, m), 7.76-7.94 (2H, m)

Reference Example 6

[0527] 2-{4-[1-(2-Methylphenyl)-1-hydroxymethyl]phenyl}-4,4-dimethyl-2-oxazoline (3.0 g), manganese dioxide (20 g) and dichloromethane (50 ml) are mixed at room temperature. The mixture is stirred at room temperature for two hours, and refluxed for three hours. The insoluble materials are removed by filtration through celite, and washed with chloroform, and the mother liquor is concentrated to give 2-[4-(2-methylbenzoyl)phenyl]-4,4-dimethyl-2-oxazoline (2.86 g) as pale yellow oil.

[0528]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.40 (6H, s), 2.33 (3H, s), 4.14 (2H, s), 7.12-7.54 (4H, m), 7.76-7.92 (2H, m), 7.95-8.14 (2H, m)

Reference Example 7

[0529] 2-[4-(2-Methylbenzoyl)phenyl]-4,4-dimethyl-2-oxazoline (2.86 g) and 4.5M hydrochloric acid (150 ml) are refluxed for 8 hours. The mixture is cooled to room temperature, and thereto is added water. The precipitates are collected by filtration to give 4-(2-methylbenzoyl)benzoic acid (2.23 g) as white powder.

[0530]¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.37 (3H, s), 7.19-7.58 (4H, m), 7.80-8.03 (2H, m), 8.10-8.35 (2H, m), 10.4 (1H, brs)

Reference Example 8

[0531] To a solution of 3-methoxy-4-trifluoromethylsulfonyloxybenzoic acid methyl ester (5 g) in toluene (200 ml) is added tetrakis(triphenylphosphine)palladium (0.9 g) under argon atmosphere, and the mixture is stirred at room temperature for five minutes. To the mixture are added (2-methylphenyl)boric acid (3.2 g), lithium chloride (1.01 g) and a 2M aqueous sodium carbonate solution (11.9 ml), and the mixture is stirred at 100° C. for two hours. To the mixture is added water, and the mixture is filtered through celite to remove the palladium. The filtrate is extracted with diethyl ether, and the ether layer is washed with water, dried, and evaporated. The residue is purified by silica gel column chromatography (solvent; n-hexane→ethyl acetate:n-hexane=1:10) to give 3-methoxy-4-(2-methylphenyl)benzoic acid methyl ester (4.07 g) as oil.

[0532]¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.12 (3H, s), 3.82 (3H, s), 3.95 (3H, s), 7.02-7.48 (5H, m), 7.63 (1H, d, J=1.51 Hz), 7.71 (1H, dd, J=1.5 Hz, 7.74 Hz)

[0533] The suitable starting compounds are treated in the same manner as in Reference Example 8 to give the compounds of Examples 22, 23 and 35-64 as mentioned below.

Reference Example 9

[0534] 2-(4-Phenyl-2-methoxyphenyl)-4,4-dimethyl-2-oxazoline (3.00 g) is dissolved in tetrahydrofuran (30 ml) under argon atmosphere, and the mixture is stirred with cooling over an ice-bath. To the mixture is added dropwise gradually an about 2M solution of 1-n-propylmagnesium bromide in tetrahydrofuran (8.0 ml) at the same temperature. After addition, the mixture is warmed to room temperature, and stirred for 16 hours. The reaction solution is stirred with cooling over an ice-bath, and thereto is added a saturated aqueous ammonium chloride solution (30 ml). The mixture is warmed to room temperature, and the organic layer is collected. The aqueous layer is extracted with ethyl acetate (30 ml×2), and the extract is combined with the organic layer, washed with a saturated aqueous sodium chloride solution (100 ml×2), dried over magnesium sulfate, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:n-hexane=1:2→1:1), and evaporated to remove the solvent to give 2-(4-phenyl-2-n-propylphenyl)-4,4-dimethyl-2-oxazoline (2.81 g) as colorless transparent viscous oil.

[0535]¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.98 (3H, t, J=11.3 Hz), 1.39 (6H, s), 1.52-1.77 (2H, m), 2.99 (2H, dd, J=7.5 Hz, J=9.5 Hz), 4.08 (2H, s), 7.30-7.51 (5H, m), 7.52-7.63 (2H, m), 7.78 (1H, d, J=6.5 Hz)

Reference Example 10

[0536] To a mixture of conc. hydrochloric acid (30 ml) and glacial acetic acid (10 ml) is added 2-(4-phenyl-2-n-propylphenyl)-4,4-dimethyl-2-oxazoline (2.70 g), and the mixture is refluxed for three days (nine hours×3). The reaction solution is concentrated to about half volume thereof under reduced pressure, and cooled over an ice-bath. The precipitated crystals are collected by filtration, and purified by silica gel column chromatography (solvent; dichloromethane→dichloromethane:methanol=50:1). The desired fractions are combined, evaporated to remove the solvent, and the crystalline residue is recrystallized from n-hexane to give 4-phenyl-2-n-propylbenzoic acid (1.67 g) as colorless needles.

[0537] M.p. 107.5-108.5° C.

Reference Example 11

[0538] To a solution of 2-(4-bromo-2-methylphenyl)-4,4-dimethyl-2-oxazoline (5 g) in dry tetrahydrofuran (40 ml) is added dropwise a 1.6M solution of n-butyl lithium in n-hexane (14.0 ml) at −70° C. The mixture is stirred at the same temperature for 30 minutes, and thereto is added dropwise cyclohexanone (2.1 ml), and the mixture is stirred for one hour. To the mixture is added water, and the mixture is evaporated to remove the tetrahydrofuran, and then extracted with diethyl ether. The diethyl ether layer is dried over anhydrous magnesium sulfate, evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=100:1˜60:1), recrystallized from acetone/n-hexane to give 2-[4-(1-hydroxy-1-cyclohexyl)-2-methylphenyl]-4,4-dimethyl-2-oxazoline (4.29 g) as white powder.

[0539]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-1.98 (11H, m), 1.38 (6H, s), 2.57 (3H, s), 4.05 (2H, s), 7.19-7.45 (2H, m), 7.72 (1H, d, J=8.1 Hz)

Reference Example 12

[0540] To a solution of 2-[4-(1-hydroxy-1-cyclohexyl)-2-methylphenyl]-4,4-dimethyl-2-oxazoline (4.29 g) in acetic acid (40 ml) is added a 10% dimethyl-2-oxazoline (4.29 g) in acetic acid (40 ml) is added a 10% precipitated crystals are collected by filtration, washed with water, and dried to give 4-cyclohexenyl-2-methylbenzoic acid (2.61 g) as white powder.

[0541]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.55-1.93 (4H, m), 2.13-2.31 and 2.32-2.56 (each 2H, each m), 2.66 (3H, s), 6.17-6.34 (1H, m), 7.15-7.42 (2H, m), 7.90-8.18 (1H, m)

Reference Example 13

[0542] To a solution of 4-cyclohexenyl-2-methylbenzoic acid (2.61 g) in ethanol (30 ml) and ethyl acetate (30 ml) is added 5% palladium-carbon (0.4 g), and the mixture is stirred at room temperature under atmospheric pressure of hydrogen gas for 30 minutes. The palladium-carbon is removed by filtration through celite, and the filtrate is evaporated to remove the solvent. The precipitated crystals are collected by filtration, crystallized from acetone/n-hexane, and washed to give 4-cyclohexyl-2-methylbenzoic acid (2.27 g) as white powder.

[0543] M.p. 129-130° C.

Reference Example 14

[0544] 4-Phenylpiperidine (0.5 g), p-fluorobenzonitrile (0.37 g) and potassium carbonate (0.78 g) are dissolved in N-methylpiperidone (5 ml), and the mixture is stirred at 120° C. for five hours. To the reaction solution is added ethyl acetate (50 ml), and the mixture is washed with water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. To the resulting residue is added methanol, and the insoluble crystals are collected by filtration, dried under reduced pressure to give 4-phenyl-1-(4-cyanophenyl)piperidine (0.39 g) as white needles.

[0545] M.p. 167-169° C.

Reference Example 15

[0546] To 4-phenyl-1-(4-cyanophenyl)piperidine (0.39 g) are added acetic acid (10 ml) and conc. hydrochloric acid (10 ml), and the mixture is refluxed for five hours. The reaction solution is concentrated, and to the residue is added diethyl ether/methanol. The insoluble crystals are collected by filtration, and dried under reduced pressure to give 4-phenyl-1-(4-carboxyphenyl)piperidine (0.39 g) as white powder.

[0547] M.p. 257-259° C. (decomposed)

Reference Example 16

[0548] Homopiperazine (100 g) is dissolved in ethanol (500 ml), and thereto is added dropwise gradually ethyl iodide (19.8 ml). The mixture is stirred at room temperature overnight, and the insoluble materials are removed by filtration. The filtrate is evaporated to remove the solvent. Purification is performed by distillation to give 1-ethylhomopiperazine (50 g) as colorless oil.

[0549] B.p. 86-88° C./37 mmHg

[0550]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.06 (3H, t, J=7.2 Hz), 1.68-1.93 (2H, m), 2.54 (2H, q, J=7.2 Hz), 2.63-2.76 (7H, m), 2.87-3.01 (2H, m)

Reference Example 17

[0551] To a solution of 4-phenyl-2-chloro-1-trifluoromethylsulfonyloxybenzene (35 g) in dimethylformamide (300 ml) are added palladium acetate (1.17 g), 1,3-bis(diphenylphosphino)propane (4.29 g), ethanol (91.5 ml) and triethylamine (29.0 ml) under carbon monooxide atmosphere, and the mixture is heated with stirring at 80-90° C. for 6 hours. To the reaction solution is added water, and further added a small amount of n-hexane. The mixture is extracted with ethyl acetate, and the ethyl acetate layer is washed with water, dried, and the residue is purified by silica gel column chromatography (solvent; n-hexane→ethyl acetate:n-hexane=1:100) to give ethyl 4-phenyl-2-chlorobenzoate (20.9 g) as colorless oil.

[0552]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.42 (3H, t, J=7.0 Hz), 4.42 (2H, q, J=7.0 Hz), 7.28-7.78 and 7.85-8.18 (all 8H, m)

[0553] The suitable starting compounds are treated in the same manner as in Reference Example 17 to give the following compounds.

Reference Example 18 Structure:

p: 1       R⁸: 2-Cl R²³: —COOCH₃ Crystalline form: Brown Oil Form: Free Reference Example 19 Structure:

p: 1       R⁸: 2-Cl R²³: —COOCH₃ Crystalline form: Brown Oil Form: Free Reference Example 20 Structure:

p: 1       R⁸: 2-Cl R²³: —COOCH₃ Crystalline form: White powder Form: Free Reference Example 21 Structure:

p: 1       R⁸: 2-Cl R²³: —COOCH₃ Crystalline form: Yellow oil Form: Free Reference Example 22 Structure:

p: 1       R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: White powder Form: Free Reference Example 23 Structure:

p: 1       R⁸: 2-NO₂ R²³: —COOCH₃ Crystalline form: Yellow viscous oil Form: Free Reference Example 24 Structure:

p: 1       R⁸: 2-Cl R²³: —COOCH₃ Crystalline form: White powder Form: Free Reference Example 25 Structure:

p: 1       R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: Pale yellow solid Form: Free Reference Example 26 Structure:

p: 1       R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: Pale yellow powder Form: Free Reference Example 27 Structure:

p: 1       R⁸: H R²³: —COOCH₃ Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 96-98° C. Form: Free Reference Example 28 Structure:

p: 1       R⁸: H R²³: —COOCH₃ Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 100-102° C. Form: Free Reference Example 29 Structure:

p: 1       R⁸: H R²³: —COOCH₃ Crystalline form: Pale brown powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 126-128° C. Form: Free Reference Example 30 Structure:

p: 1       R⁸: H R²³: —COOCH₃ Crystalline form: Brown oil Form: Free Reference Example 31 Structure:

p: 1       R⁸: H R²³: —COOCH₃ Crystalline form: Pale brown oil Form: Free Reference Example 32 Structure:

p: 1       R⁸: H R²³: —COOCH₃ Crystalline form: Pale yellow oil Form: Free Reference Example 33 Structure:

p: 1       R⁸: R²³: —COOCH₃ Crystalline form: Pale yellow oil Form: Free Reference Example 34 Structure:

p: 1       R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: Brown oil Form: Free Reference Example 35 Structure:

p: 1       R⁸: H R²³: —COOCH₃ Crystalline form: Colorless oil Form: Free Reference Example 36 Structure:

p: 1       R⁸: 2-OCH₃ R²³: —COOCH₃ Crystalline form: Slightly yellow oil Form: Free Reference Example 37 Structure:

p: 1       R⁸: 2-OCH₃ R²³: —COOCH₃ Crystalline form: Colorless oil Form: Free Reference Example 38 Structure:

p: 1       R⁸: 2-OCH₃ R²³: —COOCH₃ Crystalline form: Colorless oil Form: Free Reference Example 39 Structure:

p: 2       R⁸: 3,5-di-OCH₃ R²³: —COOCH₃ Crystalline form: Colorless prisms Form: Free Reference Example 40 Structure:

p: 1       R⁸: 3-OCH₃ R²³: —COOCH₃ Crystalline form: Colorless oil Form: Free Reference Example 41 Structure:

p: 1       R⁸: H R²³: —COOCH₃ Crystalline form: White powder Form: Free Reference Example 42 Structure:

p: 1       R⁸: 2-OCH₃ R²³: —COOCH₃ Crystalline form: Colorless oil Form: Free Reference Example 43 Structure:

p: 1       R⁸: H R²³: —CO₂C₂H₅ Crystalline form: White powder Form: Free Reference Example 44 Structure:

p: 1       R⁸: H R²³: —CO₂C₂H₅ Crystalline form: Colorless oil Form: Free Reference Example 45 Structure:

p: 1       R⁸: H R²³: —CO₂C₂H₅ Crystalline form: White powder Form: Free Reference Example 46 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: Slightly yellow oil Form: Free Reference Example 47 Structure:

p: 1       R⁸: 2-OCH₃ R²³: —CO₂CH₃ Crystalline form: White powder Form: Free Reference Example 48 Structure:

p: 1       R⁸: 2-OCH₃ R²³: —CO₂CH₃ Crystalline form: Colorless oil Form: Free Reference Example 49 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: White powder Form: Free Reference Example 50 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: White powder Form: Free Reference Example 51 Structure:

p: 1       R⁸: 3-OCH₃ R²³: —CO₂CH₃ Crystalline form: Colorless oil Form: Free Reference Example 52 Structure:

p: 2       R⁸: 3,5-di-OCH₃ R²³: —CO₂CH₃ Crystalline form: White powder Form: Free Reference Example 53 Structure:

p: 1       R⁸: 2-OCH₃ R²³: —CO₂CH₃ Crystalline form: Colorless prisms Form: Free Reference Example 54 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: Colorless oil Form: Free Reference Example 55 Structure:

p: 1       R⁸: H R²³: —CO₂CH₃ Crystalline form: White powder Form: Free Reference Example 56 Structure:

p: 1       R⁸: H R²³: —CO₂CH₃ Crystalline form: White powder Form: Free Reference Example 57 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: Colorless prisms Form: Free Reference Example 58 Structure:

p: 1       R⁸: 2-OCH₃ R²³: —CO₂CH₃ Crystalline form: Colorless oil Form: Free Reference Example 59 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: White powder Form: Free Reference Example 60 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: Slightly yellow powder Form: Free Reference Example 61 Structure:

p: 1       R⁸: 2-Cl R²³: —CO₂C₂H₅ Crystalline form: Colorless oil Form: Free Reference Example 62 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: Slightly yellow powder Form: Free Reference Example 63 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: White powder Form: Free Reference Example 64 Structure:

p: 1       R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: White powder Form: Free

[0554] The suitable starting compounds are treated in the same manner as in Reference Example 3, 7, 10 or 12 to give the following compounds.

Reference Example 65 Structure:

p: 1       R⁸: 2-Cl Crystalline form: White powder Form: Free Reference Example 66 Structure:

p: 1       R⁸: 2-Cl Crystalline form: Yellow powder Form: Free Reference Example 67 Structure:

p: 1       R⁸: 2-Cl Crystalline form: White powder Form: Free Reference Example 68 Structure:

p: 1       R⁸: 2-Cl Crystalline form: White powder Form: Free Reference Example 69 Structure:

p: 1       R⁸: H Crystalline form: White powder M.p. 257-259° C. (decomposed) Form: Free Reference Example 70 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 71 Structure:

p: 1       R⁸: H Crystalline form: Brown powder M.p. 233-235° C., Form: Free Reference Example 72 Structure:

p: 1       R⁸: 2-C₂H₅ Crystalline form: Colorless plates Solvent for recrystallization: n-Hexane/chloroform M.p. 164-165° C. Form: Free Reference Example 73 Structure:

p: 1       R⁸: 2-n-C₃H₇ Crystalline form: Colorless needles Solvent for recrystallization: n-Hexane M.p. 107.5-108.5° C. Form: Free Reference Example 74 Structure:

p: 1       R⁸: 2-NO₂ Crystalline form: Red brown powder M.p. 199-201° C. Form: Free Reference Example 75 Structure:

p: 1       R⁸: 2-Cl Crystalline form: White powder Form: Free Reference Example 76 Structure:

p: 1       R⁸: 2-Cl Crystalline form: White powder Form: Free Reference Example 77 Structure:

p: 1       R⁸: 2-Cl Crystalline form: Slightly red powder Form: Free Reference Example 78 Structure:

p: 1       R⁸: H Crystalline form: White powder Form: Free Reference Example 79 Structure:

p: 1       R⁸: H Crystalline form: White powder Form: Free Reference Example 80 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Form: Hydrochloride Reference Example 81 Structure:

p: 1       R⁸: H Crystalline form: Brown powder Form: Free Reference Example 82 Structure:

p: 1       R⁸: 2-OCH₃ Crystalline form: Pale brown powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 133-135° C. Form: Free Reference Example 83 Structure:

p: 1       R⁸: 3-OCH₃ Crystalline form: Brown powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 126-128° C. Form: Free Reference Example 84 Structure:

p: 1       R⁸: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 198-201° C. Form: Free Reference Example 85 Structure:

p: 1       R⁸: H Crystalline form: White powder Solvent for recrystillization: Chloroform/diethyl ether M.p. 236-239° C. Form: Free Reference Example 86 Structure:

p: 1       R⁸: H Crystalline form: White needles Solvent for recrystallization: Methanol/diethyl ether M.p. 257-260° C. Form: Free Reference Example 87 Structure:

p: 1       R⁸: H Crystalline form: Pale brown powder Solvent for recrystallization: Methanol/diethyl ether M.p. 201-203° C. Form: Free Reference Example 88 Structure:

p: 1       R⁸: H Crystalline form: White powder Solvent for recrystallization: Methanol/diethyl ether M.p. 230° C. (decomposed) Form: Hydrochloride Reference Example 89 Structure:

p: 1       R⁸: H Crystalline form: White powder Solvent for recrystallization: Methanol/diethyl ether M.p. 206-207° C. Form: Hydrochloride Reference Example 90 Structure:

p: 1       R⁸: H Crystalline form: Pale yellow powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 266-269° C. Form: Hydrochloride Reference Example 91 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: Pale yellow powder Solvent for recrystallization: Methanol M.p. 276-279° C. Form: Hydrochloride Reference Example 92 Structure:

p: 1       R⁸: H Crystalline form: White powder Solvent for recrystallization: Methanol/diethyl ether M.p. 161-163° C. Form: Free Reference Example 93 Structure:

Crystalline form: Pale yellow powder Solvent for recrystallization: Methanol/diethyl ether Mp.p 250-251° C. Form: Free Reference Example 94 Structure:

p: 1       R⁸: H Crystalline form: Yellow amorphous Form: Free Reference Example 95 Structure:

p: 1       R⁸: H Crystaqlline form: White needles Form: Free Reference Example 96 Structure:

p: 1       R⁸: H Crystalline form: Pale yellow needles Solvent for recrystallization: Methanol/diethyl ether M.p. 309-311° C. Form: Hydrochloride Reference Example 97 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 198-200° C. Form: Free Reference Example 98 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 99 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 100 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 208° C. Form: Free Reference Example 101 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane Mp.p 234-236° C. Form: Free Reference Example 102 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 103 Structure:

p: 1       R⁸: 2-OCH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 132-133° C. Form: Free Reference Example 104 Structure:

p: 1       R⁸: 2-OCH₃ Crystalline form: Colorless prisms Solvent for recrystallization: Ethyl acetate M.p. 153-154° C. Form: Free Reference Example 105 Structure:

p: 1       R⁸: 2-OCH₃ Crystalline form: Colorless prisms Solvent for recrystallization: Ethyl acetate M.p. 118-119° C. Form: Free Reference Example 106 Structure:

p: 2       R⁸: 3,5-di-OCH₃ Crystalline form: White powder Solvent for recrystillization: Acetone/n-hexane M.p. 239-240° C. Form: Free Reference Example 107 Structure:

p: 1       R⁸: 3-OCH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 179-182° C. Form: Free Reference Example 108 Structure:

p: 1       R⁸: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 194-197° C. Form: Free Reference Example 109 Structure:

p: 1       R⁸: 2-OCH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 149-150° C. Form: Free Reference Example 110 Structure:

p: 1       R⁸: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 202-204° C. Form: Free Reference Example 111 Structure:

p: 1       R⁸: H Crystalline form: White powder Form: Free Reference Example 112 Structure:

p: 1       R⁸: 2-OCH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 134-135° C. Form: Free Reference Example 113 Structure:

p: 1       R⁸: 2-OCH₃ Crystalline form: White powder Form: Free Reference Example 114 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 115 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 262-265° C. Form: Free Reference Example 116 Structure:

p: 1       R⁸: 3-OCH₃ Crystalline form: White powder Form: Free Reference Example 117 Structure:

p: 1       R⁸: 3-OCH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 146-147° C. Form: Free Reference Example 118 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 132-133° C. Form: Free Reference Example 119 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 129-130° C. Form: Free Reference Example 120 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 121 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: Pale yellow powder Form: Free Reference Example 122 Structure:

p: 1       R⁸: H Crystalline form: White powder Form: Free Reference Example 123 Structure:

p: 1       R⁸: H Crystalline form: White powder Form: Free Reference Example 124 Structure:

p: 2       R⁸: 3,5-di-OCH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 231-232° C. Form: Free Reference Example 125 Structure:

p: 1       R⁸: 2-OCH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 159-160° C. Form: Free Reference Example 126 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 117-118° C. Form: Free Reference Example 127 Structure:

p: 1       R⁸: H Crystalline form: White powder Solvent for recrystaillization: Ethanol/diethyl ether M.p. 246-248° C. Form: Free Reference Example 128 Structure:

p: 1       R⁸: H Crystalline form: Colorless prisms Solvent for recrystallization: Acetone/n-hexane M.p. 185-187° C. Form: Free Reference Example 129 Structure:

p: 1       R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 130 Structure:

p: 1       R⁸: 2-OCH₃ Crystalline form: White powder Solvent for recrystaillization: Acetone/n-hexane M.p. 145-148° C. Form: Free Reference Example 131 Structure:

p: 1       R⁸: 2-Cl Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 164° C. Form: Free

[0555] The suitable starting compounds are treated in the same manner as in Reference Example 17 to give the following compounds. Reference Example 132 Structure:

Crystalline form: White needles ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.97 (3H, s), 7.48-7.62 (3H, m), 7.81 (1H, dd, J = 8.0 Hz, J = 0.8 Hz), 7.98-8.17 (2H, m), 8.34 (1H, dd, J = 8.0 Hz, J = 2.2 Hz), 9.28 (1H, dd, J = 2.2 Hz, J = 0.8 Hz) Form: Free Reference Example 133 Structure:

Crystalline form: White powder ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.38 (3H, s), 3.98 (3H, s), 7.19-7.50 (4H, m), 7.50 (1H, dd, J = 8.0 Hz, J = 0.8 Hz), 8.35 (1H, dd, J = 8.0 Hz, J = 2.0 Hz), 9.30 (1H, dd, J = 2.0 Hz, J = 0.8 Hz) Form: Free Reference Example 134 Structure:

Crystalline form: Pale brown powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 110-111° C. Form: Free

[0556] The suitable starting compounds are treated in the same manner as in Reference Example 3, 7, 10 or 12 to give the following compounds. Reference Example 135 Structure:

Crystalline form: Colorless needles M.p. 191-192° C. Form: Free Reference Example 136 Structure:

Crystalline form: Colorless needles M.p. 228-230° C. Form: Free Reference Example 137 Structure:

Crystalline form: Pale brown needles Solvent for recrystallization: Methanol/diethyl ether M.p. 253-255° C. Form: Hydrochloride

[0557] The suitable starting compounds are treated in the same manner as in Reference Example 17 to give the following compounds.

Reference Example 138 Structure:

p: 1 R⁸: H R²³: —CO₂C₂H₅ Crystalline form: White powder ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 6.80-6.95 (1H, m), 7.20-7.35 (1H, m), 7.55-7.65 (1H, m), 7.98-8.16 (4H, m), 8.45-8.60 (2H, m), 1.34 (3H, t, J = 7.2 Hz), 4.33 (2H, q, J = 7.2 Hz) Reference Example 139 Structure:

p: 1 R⁸: H R²³: —CO₂C₂H₅ Crystalline form: White powder ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.34 (3H, t, J = 7.2 Hz), 2.29 (3H, s), 4.33 (2H, q, J = 7.2 Hz), 7.10-7.20 (1H, m), 7.50-7.58 (1H, m), 7.95-8.15 (4H, m), 8.33 (1H, s), 8.43 (1H, s) Reference Example 140 Structure:

p: 1 R⁸: H R²³: —CO₂C₂H₅ Crystalline form: White powder ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.40 (3H, t, J = 7.2 Hz), 4.21 (2H, s), 4.37 (2H, q, J = 7.2 Hz), 7.60- 7.70 (2H, m), 8.00-8.11 (2H, m), 8.42 (1H, brs) Reference Example 141 Structure:

p: 1 R⁸: 2-CH₃ R²³: —CO₂CH₃ Crystalline form: White powder ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.61 (3H, s), 3.88 (3H, s), 4.20 (2H, s), 7.40-7.55 (2H, m), 7.90-8.01 (1H, m), 8.30 (1H, brs)

[0558] The suitable starting compounds are treated in the same manner as in Reference Example 3, 7, 10 or 12 to give the following compounds.

Reference Example 142 Structure:

p: 1 R⁸: H Crystalline form: White powder ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 7.40-7.55 (1H, m), 7.85-8.03 (2H, m), 8.03-8.25 (4H, m), 8.85-9.00 (2H, m), 12.4-14.1 (1H, brs) Reference Example 143 Structure:

p: 1 R⁸: H Crystalline form: White powder ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.41 (3H, s), 7.75-7.95 (2H, m), 7.95-8.25 (4H, m), 8.70 (1H, s), 8.85 (1H, s), 12.6-13.6 (1H, brs) Reference Example 144 Structure:

p: 1 R⁸: H Crystalline form: Light brown powder ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.07 (6H, s), 5.94 (2H, s), 7.30-7.40 (2H, m), 8.20-8.30 (2H, m), 10.7-12.1 (1H, brs)

[0559] The data of NMR analysis of the compounds of the above Reference Examples are as follows.

[0560] The suitable starting compounds are treated in the same manner as in Reference Example 17 to give the following compounds.

Reference Example 145 Structure:

p: 1 R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: Pale yellow oil Form: Free Reference Example 146 Structure:

p: 1 R⁸: 2-Cl R²³: —COOCH₃ Crystalline form: Yellow prisms Form: Free Reference Example 147 Structure:

p: 1 R⁸: 2-Cl R²³: —COOCH₃ Crystalline form: Yellow needles Form: Free Reference Example 148 Structure:

p: 1 R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: Colorless viscous oil Form: Free Reference Example 149 Structure: R⁹: 4-OH p: 1 R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: White powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 97-98.5° C. Form: Free Reference Example 150 Structure: R⁹: 4-OCH(CH₃)₂ p: 1 R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: Colorless viscous oil Form: Free Reference Example 151 Structure: R⁹: 4-O(CH₂)₃CH₃ p: 1 R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: Colorless viscous oil Form: Free Reference Example 152 Structure: R⁹: 4-OCH₂CH(CH₃)₂ p: 1 R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: Colorless viscous oil Form: Free Reference Example 153 Structure: R⁹: 4-NHCOCF₃ p: 1 R⁸: 2-Cl R²³: —COOCH₃ Crystalline form: White powder Form: Free Reference Example 154 Structure: R⁹: 4-OCH₂COOH p: 1 R⁸: 2-CH₃ R²³: —COOCH₃ Crystalline form: White powder Solvent for recrystallization: Dichloromethane/n-hexane Form: Free Reference Example 156 Structure:

p: 1 R⁸: 2-Cl R²³: —COOCH₃ Solvent for recrystallization: Ethyl acetate/n-hexane M.p. 118-123° C. Form: Free Reference Example 157 Structure:

p: 1 R⁸: 3-OCH₃ R²³: —COOCH₃ Crystalline form: White powder Form: Free Reference Example 158 Structure:

p: 1 R⁸: 3-OCH₃ R²³: —COOCH₃ Crystalline form: White powder Form: Free Reference Example 159 Structure:

p: 1 R⁸: 3-OCH₃ R²³: —COOCH₃ Crystalline form: Colorless oil Form: Free Reference Example 160 Structure:

p: 1 R⁸: 3-OCH₃ R²³: —COOCH₃ Reference Example 161 Structure: R⁹: 4-NHCOO(CH₂)₂C(CH₃)₃ p: 1 R⁸: 2-OCH₃ R²³: —COOCH₃ Crystalline form: Colorless oil Form: Free The suitable starting compounds are treated in the same manner as in Reference Example 3, 7, 10 or 12 to give the following compounds.

Reference Example 162 Structure:

p: 1 R⁸: 2-CH₃ Crystalline form: Pale brown powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Reference Example 163 Structure:

p: 1 R⁸: 2-CH₃ Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether Form: Hydrochloride Reference Example 164 Structure:

p: 1 R⁸: 2-Cl Crystalline form: White powder Form: Hydrochloride Reference Example 165 Structure:

p: 1 R⁸: 2-Cl Crystalline form: White powder Form: Free Reference Example 166 Structure:

p: 1 R⁸: 2-CH₃ Crystalline form: White powder Solvent for recrystallization: Ethyl acetate/n-hexane M.p. 127.5-130° C. Form: Free Reference Example 167 Structure: R⁹: 4-OCH(CH₃)₂ p: 1 R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 168 Structure: R⁹: 4-O(CH₂)₃CH₃ p: 1 R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 169 Structure: R⁹: 4-OCH₂CH(CH₃)₂ p: 1 R⁸: 2-CH₃ Crystalline form: Pale yellow powder Form: Free Reference Example 170 Structure:

p: 1 R⁸: 2-Cl Crystalline form: White powder Form: Free Reference Example 171 Structure:

p: 1 R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 172 Structure:

p: 1 R⁸: 2-Cl Crystalline form: White powder Form: Free Reference Example 174 Structure: R⁹: 4-CH₂CH(CH₃)₂ p: 1 R⁸: 2-CH₃ Crystalline form: White powder Form: Free Reference Example 175 Structure:

p: 1 R⁸: 2-CH₃ Crystalline form: Yellow powder Form: Free Reference Example 176 Structure:

p: 1 R⁸: 3-OCH₃ Crystalline form: White powder Form: Free Reference Example 177 Structure:

p: 1 R⁸: 3-OCH₃ Crystalline form: White powder M.p. 170-171° C. Form: Free Reference Example 178 Structure:

p: 1 R⁸: 3-OCH₃ Crystalline form: White powder M.p. 128-129° C. Form: Free Reference Example 179 Structure:

p: 1 R⁸: 3-OCH₃ Crystalline form: White powder M.p. 146-147° C. Form: Free Reference Example 180 Structure: R⁹: 4-NHCOO(CH₂)₂C(CH₃)₃ p: 1 R⁸: 2-OCH₃ Crystalline form: White powder Form: Free

[0561] The data of NMR analysis of the compounds of the above Reference Examples are as follows.

[0562] NMR analysis:

[0563] The compound of Reference Example 18 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.90-3.06 [all 9H, m, 2.38 (s)], 3.30-3.72 (4H, m), 3.85 (3H, s), 6.34-6.81 [all 2H, m, 6.53 (dd, J=8.93 Hz, J=8.99 Hz), 6.67 (d, J=2.32 Hz)], 7.83 (1H, d, J=8.95 Hz)

[0564] The compound of Reference Example 19 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.92-3.60 (all 8H, m), 3.88 (3H, s), 6.79-7.48 and 7.78-7.79 [all 8H, m, 6.79 (dd, J=8.92 Hz, J=8.92 Hz)]

[0565] The compound of Reference Example 20 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.68-2.09 [all 4H, m, 1.77 (d, J=3.30 H), 1.84 (d, J=4.20 Hz)], 2.61-3.12 (all 3H, m), 3.75-4.10 [all 5H, m, 3.87 (s)], 6.78 (1H, dd, J=8.96 Hz, J=8.97 Hz), 6.92 (1H, d, J=2.58 Hz), 7.15-7.41 (all 5H, m), 7.86 (1H, d, J=8.92 Hz)

[0566] The compound of Reference Example 21 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.57 (3H, t, J=5.21 Hz), 3.31 (3H, t, J=5.23 Hz), 3.55 (2H, s), 3.86 (3H, s), 6.72 (1H, dd, J=8.95 Hz, J=8.94 Hz), 6.85 (1H, d, J=2.56 Hz), 7.19-7.49 (5H, m), 7.82 (1H, d, J=8.91 Hz)

[0567] The compound of Reference Example 22 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.66 (3H, s), 3.85 (3H, s), 3.89 (3H, s), 6.81-7.60 (6H, m), 7.85-8.08 (1H, m)

[0568] The compound of Reference Example 23 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.94 (3H, s), 7.39-7.70 (5H, m), 7.79-7.92 (2H, m), 8.02-8.11 (1H, m)

[0569] The compound of Reference Example 24 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 3.4-3.55 (2H, m), 3.8 (3H, s), 3.8-3.95 (2H, m), 7.36 (1H, s), 7.50 (1H, dd, J=8.8 Hz, J=2 Hz), 7.82 (1H, d, J=8.8 Hz), 7.86 (1H, d, J=2 Hz)

[0570] The compound of Reference Example 25 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.67 (3H, s), 3.93 (3H, s), 7.22-7.43 (3H, m), 7.95-8.08 (1H, m), 8.48-8.63 (1H, m), 8.65-8.75 (1H, m)

[0571] The compound of Reference Example 26 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.69 (3H, s), 3.93 (3H, s), 7.41-7.63 (4H, m), 7.95-8.08 (1H, m), 8.62-8.76 (2H, m)

[0572] The compound of Reference Example 30 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.88 (3H, t, J=7.4 Hz), 1.05 (3H, t, J=7.4 Hz), 1.80 (3H, hept, J=7.4 Hz), 4.00 (2H, t, J=7.4 Hz), 4.31 (3H, t, J=7.4 Hz), 7.06 (1H, d, J=1.1 Hz), 7.17 (1H, d, J=1.1 Hz), 7.60-7.76 (2H, m), 8.06-8.22 (2H, m)

[0573] The compound of Reference Example 31 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.68 (3H, s), 7.20-7.36 (1H, m), 7.40-7.66 (4H, m), 7.66-7.90 (2H, m), 8.58-8.74 (1H, m)

[0574] The compound of Reference Example 32 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.96 (3H, s), 7.22-7.35 (1H, m), 7.56 (1H, t, J=7.8 Hz), 7.72-7.86 (2H, m), 8.09 (1H, dt, J=1.5 Hz, J=7.8 Hz), 8.24 (1H, ddd, J=1.2 Hz, J=1.8 Hz, J=7.8 Hz), 8.65 (1H, t, J=1.6 Hz), 8.69-8.77 (1H, m)

[0575] The compound of Reference Example 33 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 3.96 (3H, s), 7.39 (1H, ddd, J=0.8 Hz, J=4.8 Hz, J=7.8 Hz), 7.57 (1H, t, J=7.8 Hz), 7.75-7.83 (1H, m), 7.87-7.97 (1h, m), 8.08 (1H, dt, J=1.3 Hz, J=7.8 Hz), 8.27 (1H, t, J=1.6 Hz), 8.63 (1H, dd, J=1.6 Hz, J=4.8 Hz), 8.88 (1H, dd, J=0.7 Hz, J=2.4 Hz)

[0576] The compound of Reference Example 34 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 2.69 (3H, s), 3.92 (3H, s), 7.32-7.53 (3H, m), 7.89 (1H, ddd, J=1.7 Hz, J=2.3 Hz, J=7.1 Hz), 8.03 (1H, d, J=8.6 Hz), 8.63 (1H, dd, J=1.6 Hz, J=4.8 Hz), 8.86 (1H, dd, J=0.7 Hz, J=1.6 Hz)

[0577] The compound of Reference Example 35 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 3.95 (3H, s), 7.32-7.56 (4H, m), 7.59-7.66 (2H, m), 7.75-7.83 (1H, m), 7.99-8.07 (1H, m), 8.25-8.33 (1H, m)

[0578] The compound of Reference Example 36 ¹H-NMR (200 MHz, CDCl₃) Δ ppm: 2.27 (3H, s), 3.91 (3H, s), 3.92 (3H, s), 6.86-7.04 (2H, m), 7.16-7.41 (4H, m), 7.76-7.96 (1H, m)

[0579] The compound of Reference Example 37 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.81, 3.90 and 3.93 (each 3H, each s), 6.87-7.23 (4H, m), 7.29-7.52 (2H, m), 7.76-7.92 (1H, m)

[0580] The compound of Reference Example 38 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.91 and 3.97 (each 3H, each s), 7.11-7.28 (2H, m), 7.32-7.55 (3H, m), 7.56-7.70 (2H, m), 7.89 (1H, d, J=8.0 Hz

[0581] The compound of Reference Example 39 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.39 (3H, s), 3.79 (6H, s), 3.95 (3H, s), 7.23 (4H, s), 7.33 (2H, s)

[0582] The compound of Reference Example 40 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.87 and 3.94 (each 3H, each s), 7.21-7.50 (4H, m), 7.51-7.61 (2H, m), 7.62-7.83 (2H, m)

[0583] The compound of Reference Example 41 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.43 and 3.94 (each 3H, each s), 7.08-7.29 (1H, m), 7.30-7.50 (3H, m), 7.58-7.72 (2H, m), 8.02-8.18 (2H, m)

[0584] The compound of Reference Example 42 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.24, 2.37, 3.90 and 3.91 (each 3H, each s), 6.78-6.98 (2H, m), 7.00-7.19 (3H, m), 7.73-7.90 (1H, m)

[0585] The compound of Reference Example 43 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.42 (3H, t, J=7.1 Hz), 4.41 (2H, q, J=7.1 Hz), 7.27-7.90 and 8.02-8.22 (all 13H, m)

[0586] The compound of Reference Example 44 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.37 (3H, t, J=7.1 Hz), 4.34 (2H, q, J=7.1 Hz), 7.01-7.31 and 7.32-7.68 (all 11H, m), 7.79-8.00 (2H, m)

[0587] The compound of Reference Example 45 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.47 (3H, t, J=7 Hz), 4.41 (2H, q, J=7 Hz), 7.29-7.57, 7.58-7.84 and 8.03-8.21 (all 13H, m)

[0588] The compound of Reference Example 46 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.42 (3H, s), 2.67 (3H, s), 3.91 (3H, s), 7.07-7.59 (6H, m), 7.87-8.11 (1H, m)

[0589] The compound of Reference Example 47 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.91, 3.94, 3.97 and 3.98 (each 3H, each s), 6.96 (1H, d, J=8.3 Hz), 7.03-7.24 (4H, m), 7.88 (1H, d, J=7.9 Hz)

[0590] The compound of Reference Example 48 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.43, 3.91 and 3.98 (each 3H, each s), 7.04-7.29 (3H, m), 7.30-7.51 (3H, m), 7.88 (1H, d, J=7.9 Hz)

[0591] The compound of Reference Example 49 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.67 (3H, s), 3.86 (3H, s), 3.90 (3H, s), 6.90-7.08 (2H, m), 7.35-7.49 (2H, m) and 7.50-7.66 (2H, m), 7.89-8.07 (1H, m)

[0592] The compound of Reference Example 50 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.69 (3H, s), 3.92 (3H, s), 7.27-7.81 and 7.95-8.11 (all 12H, m)

[0593] The compound of Reference Example 51 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.12 (3H, s), 3.82 (3H, s), 3.95 (3H, s), 7.02-7.48 (5H, m), 7.63 (1H, d, J=1.4 Hz), 7.71 (1H, dd, J=7.7 Hz, J=1.4 Hz)

[0594] The compound of Reference Example 52

[0595]¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.05 (3H, s), 3.77 (6H, s), 3.96 (3H, s), 7.03-7.18 (1H, m), 7.19-7.32 (3H, m), 7.34 (2H, s)

[0596] The compound of Reference Example 53 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.40, 3.90 and 3.97 (each 3H, each s), 7.09-7.34 (4H, m), 7.42-7.59 (2H, m), 7.87 (1H, d, J=7.9 Hz)

[0597] The compound of Reference Example 54 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.26, 2.65 and 3.91 (each 3H, each s), 7.08-7.38 (6H, m), 7.89-8.02 (1H, m)

[0598] The compound of Reference Example 55 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.41 and 3.93 (each 3H, each s), 7.17-7.34 (2H, m), 7.46-7.57 (2H, m), 7.82-7.72 (2H, m), 8.02-8.16 (2H, m)

[0599] The compound of Reference Example 56

[0600]¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.26 and 3.94 (each 3H, each s), 7.14-7.35 (4H, m), 7.36-7.52 (2H, m), 7.99-8.18 (2H, m)

[0601] The compound of Reference Example 57

[0602]¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.68 (3H, s), 3.91 (3H, s), 7.29-7.54 and 7.55-7.72 (all 7H, m), 7.91-8.08 (1H, m)

[0603] The compound of Reference Example 58 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.04 (6H, s), 3.88 and 3.92 (each 3H, each s), 6.71-6.85 (2H, m), 7.06-7.48 (3H, m), 7.78-7.93 (1H, m)

[0604] The compound of Reference Example 59

[0605]¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.66 (3H, s), 3.90 (3H, s), 5.12 (2H, s), 6.98-7.12 (2H, m), 7.20-7.68 (10H, m)

[0606] The compound of Reference Example 60 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.70 (3H, s), 3.93 (3H, s), 7.38-7.58 (2H, m), 7.68-7.87 (2H, m), 7.98-8.12 (1H, m), 8.21-8.46 (2H, m)

[0607] The compound of Reference Example 61 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.42 (3H, t, J=7.0 Hz), 4.42 (2H, q, J=7.0 Hz), 7.28-7.78 and 7.85-8.18 (all 8H, m)

[0608] The compound of Reference Example 62 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.40 (3H, s), 2.67 (3H, s), 3.90 (3H, s), 7.18-7.31 (2H, m), 7.37-7.58 (4H, m), 7.91-8.05 (1H, m)

[0609] The compound of Reference Example 63 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.44 (3H, t, J=7.0 Hz), 2.66 (3H, s), 3.90 (3H, s), 4.10 (2H, q, J=7.0 Hz), 6.88-7.06 (2H, m), 7.34-7.49 (2H, m), 7.50-7.64 (2H, m), 7.89-8.06 (1H, m)

[0610] The compound of Reference Example 64 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.06 (3H, t, J=7.4 Hz), 1.70-1.97 (2H, m), 2.66 (3H, m), 3.97 (2H, d, J=6.5 Hz), 6.89-7.08 (2H, m), 7.35-7.48 (2H, m), 7.49-7.64 (2H, m), 7.89-8.08 (1H, m)

[0611] The compound of Reference Example 65 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.40-2.90 and 3.21-3.90 [all 13H, m, 2.33 (s)], 6.50-8.40 [all 4H, m, 7.71 (d, J=8.41 Hz)]

[0612] The compound of Reference Example 66 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.85-4.90 (all 9H, m), 6.79-7.38 and 7.45-7.69 (all 7H, m)

[0613] The compound of Reference Example 68 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.60-4.75 (all 11H, m), 6.80-7.85 [all 8H, m, 7.77 (d, J=8.80 Hz)]

[0614] The compound of Reference Example 70 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.74 (3H, s), 3.88 (3H, s), 5.82-8.39 [all 8H, m, 6.95 (d, J=8.0 Hz), 8.15 (d, J=8.52 Hz)]

[0615] The compound of Reference Example 75 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.77 (3H, s), 3.42-3.50 (2H, m), 3.78-3.86 (2H, m), 7.49 (1H, dd, J=8.8 Hz, J=2.2 Hz), 7.83 (1H, d, J=8.8 Hz), 7.84 (1H, d, J=2.2 Hz), 12.6-13.3 (1H, m)

[0616] The compound of Reference Example 76 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.86 (6H, d, J=6.6 Hz), 1.8-2.05 (1H, m), 3.0 (2H, d, J=7.2 Hz), 3.4-3.55 (2H, m), 3.8-3.95 (2H, m), 7.49 (1H, dd, J=8.8 Hz, J=2.2 Hz), 7.83 (1H, d, J=8.8 Hz), 7.85 (1H, d, J=2.2 Hz), 12.8-13.1 (1H, m)

[0617] The compound of Reference Example 77 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 3.3-3.41 (2H, m), 3.75-3.95 (2H, m), 4.39 (2H, s), 7.2-7.45 (5H, m), 7.5 (1H, dd, J=9 Hz, J=2.2 Hz), 7.84 (1H, d, J=9 Hz), 7.88 (1H, d, J=2.2 Hz)

[0618] The compound of Reference Example 78 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.93 (3H, s), 4.56 (2H, s), 7.20-7.50 (5H, m), 7.62 (2H, d, J=8.7 Hz), 7.81 (2H, d, J=8.7 Hz), 8.76 (1H, s)

[0619] The compound of Reference Example 79 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 7.38-7.51 (1H, m), 7.51-7.95 (4H, m), 7.95-8.10 (1H, m), 8.68-8.95 (2H, m), 10.3-13.5 (1H, br)

[0620] The compound of Reference Example 80 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.58 (3H, s), 7.38-7.48 (2H, m), 7.48-7.64 (1H, m), 7.46-8.01 (1H, m), 8.63 (1H, d, J=5.0 Hz), 8.80 (1H, s)

[0621] The compound of Reference Example 81 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.22 (3H, s), 2.30-2.58 (4H, m), 3.15-3.40 (4H, m), 6.85-7.05 (2H, m), 7.15-7.84 (2H, m), 11.75-12.80 (1H, brs)

[0622] The compound of Reference Example 94 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.77 (3H, t, J=7.3 Hz), 1.75 (2H, q, J=7.3 Hz), 4.15 (2H, t, J=7.3 Hz), 7.31-7.97 (3H, m), 8.02 (1H, d, J=1.7 Hz), 8.11-8.27 (2H, m)

[0623] The compound of Reference Example 95 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 7.19 (1H, s), 7.35-7.64 (2H, m), 7.69 (1H, s), 8.00-8.30 (4H, m), 10.40-11.62 (1H, brs)

[0624] The compound of Reference Example 98 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.55-1.94 (4H, m), 2.13-2.30 (2H, m), 2.31-2.56 (2H, m), 2.66 (3H, s), 6.18-6.35 (1H, m), 7.15-7.42 (2H, m), 7.90-8.18 (1H, m)

[0625] The compound of Reference Example 99 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.62 (3H, s), 7.58-7.82 (2H, m), 7.88-8.19 (3H, m), 8.21-8.48 (2H, m), 12.97 (1H, s)

[0626] The compound of Reference Example 102 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.42-2.00 (6H, m), 2.18-2.46 (2H, m), 2.47-2.79 (3H, s), 6.21 (1H, t, J=6.7 Hz), 7.05-7.40 (1H, m), 7.88-8.12 (1H, m)

[0627] The compound of Reference Example 111 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 7.03-7.31 (7H, m), 7.32-7.58 (4H, m), 7.95 (2H, d, J=8.35 Hz)

[0628] The compound of Reference Example 113 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.30 and 4.15 (each 3H, each s), 7.09-7.48 (6H, m), 8.23 (1H, d, J=8.1 Hz), 10.0-11.42 (1H, m)

[0629] The compound of Reference Example 114 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.73 and 3.87 (each 3H, each s), 7.00 and 7.59 (each 2H, each dd, J=8.8 Hz, J=2.1 Hz), 7.36-7.52 (2H, m), 8.03-8.21 (1H, m)

[0630] The compound of Reference Example 116 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.14 and 3.85 (each 3H, each s), 7.09-7.41 (5H, m), 7.71 (1H, d, J=1.4 Hz), 7.82 (1H, dd, J=8.0 Hz, J=1.5 Hz)

[0631] The compound of Reference Example 120 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.21-2.06 and 2.48-2.82 (all 13H, m), 2.63 (3H, s), 4.84-6.49 (1H, m), 6.98-7.19 (2H, m), 7.99 (1H, d, J=8.7 Hz)

[0632] The compound of Reference Example 121 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.40-2.23 and 2.87-3.14 (all 9H, m), 2.64 (3H, s), 6.98-7.24 (2H, m), 8.00 (1H, d, J=8.7 Hz)

[0633] The compound of Reference Example 122 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.49-1.88 (4H, m), 2.08-2.19 and 2.20-2.52 (each 2H, each m), 6.20-6.40 (1H, m), 7.51 and 7.87 (each 2H, each d, each J=8.4 Hz), 12.42-13.18 (1H, m)

[0634] The compound of Reference Example 123 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.49-1.68 (4H, m), 1.69-1.91 (2H, m), 2.18-2.37 (2H, m), 2.45-2.67 (2H, m), 6.23 (1H, t,J=6.7 Hz), 7.42 and 7.86 (each 2H, each d, each J=8.4 Hz), 7.28-7.79 (1H, m)

[0635] The compound of Reference Example 129 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.75 (3H, m), 7.29-7.74 (7H, m), 8.10-8.22 (1H, m)

[0636] The compound of Reference Example 153 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.94 (s, 3H), 7.58 (dd, J=8.6, 2.2 Hz, 1H), 7.78 (d, J=2.2 Hz, 1H), 7.90 (d, J=8.6 Hz, 1H), 8.32 (1H, brs)

[0637] The compound of Reference Example 145 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.70 (3H, s), 3.92 (3H, s), 7.22-7.35 (1H, m), 7.70-7.96 (4H, m), 8.03 (1H, d, J=8.2 Hz), 8.67-8.78 (1H, m)

[0638] The compound of Reference Example 157 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.88 (3H, s), 3.41-3.50 (2H, m), 3.79-3.89 3.89 (3H, s), 3.90 (3H, s), 7.49 (1H, d, J=8.2 Hz), 7.87 (1H, d, J=1.7 Hz), 7.65 (1H, dd, J=8.2 Hz, 1.7 Hz)

[0639] The compound of Reference Example 158 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.77, 3.83, 3.93 (each 3H, eash s), 6.89-7.08 (2H, m), 7.15-7.44 (3H, m), 7.54-7.79 (2H, m)

[0640] The compound of Reference Example 159 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.84, 3.88, 3.94 (each 3H, each s), 6.83-6.98 (1H, m), 7.02-7.15 (2H, m), 7.27-7.43 (2H, m), 7.64 (1H, d, J=1.4 Hz), 7.71 (1H, dd, J=1.6 Hz, J=7.8 Hz)

[0641] The compound of Reference Example 162 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.55 (3H, s), 4.53 (2H, s), 4.55 (2H, s), 7.25-7.55 (7H, m), 7.88 (1H, d, J=9 Hz), 12.88 (1H, s)

[0642] The compound of Reference Example 163 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.62 (3H, s), 7.70-7.82 (1H, m), 7.90-8.13 (3H, m), 8.20-8.40 (2H, m), 8.72-8.86 (1H, m)

[0643] The compound of Reference Example 170 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.97 (6H, d, J=6.6 Hz), 1.23 (3H, t, J=7.0 Hz), 1.85-2.10 (1H, m), 3.13 (2H, d, J=7.5 Hz), 3.39 (2H, q, J=7 Hz), 6.54 (1H, s), 7.36 (1H, dd, J=8.7 Hz, J=2.2 Hz), 7.63 (1H, d, J=2.2 Hz), 7.98 (1H, d, J=8.7 Hz)

[0644] The compound of Reference Example 171 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.57 (3H, s), 5.17 (2H, s), 6.58-6.92, 6.93-8.03 (total 12H, m), 12.56-12.94 (1H, m)

[0645] The compound of Reference Example 173 ¹H-NMR (250 MHz, DMSO-d₆) δ ppm: 2.84 (2H, t, J=4.6 Hz), 3.70 (2H, t, J=4.6 Hz), 4.64 (2H, s), 7.17 (4H, s), 7.54 (1H, dd, J=7 Hz, J=1.6 Hz), 7.76-7.83 (2H, m), 9.01 (1H, s)

[0646] The compound of Reference Example 175 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.61 (3H, s), 4.10-5.40 (2H, brs), 7.32-7.90 (4H, m), 7.95 (1H, d, J=8.2 Hz), 9.22 (1H, d, J=5.8 Hz)

[0647] The compound of Reference Example 176 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.86 (2H, t, J=5.8 Hz), 3.67 (2H, t, J=5.8 Hz), 3.89 (3H, s), 4.63 (2H, s), 7.18 (4H, s), 7.4-7.95 (1H, d, J=8.2 Hz)

[0648] The compound of Reference Example 174 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.83 (6H, d, J=6.6 Hz), 1.68-1.97 (1H, m), 2.42 (2H, d, J=7.2 Hz), 2.48 (3H, s), 6.93-7.13 (2H, m), 7.74 (1H, d, J=8.5 Hz)

[0649] The compound of Reference Example 146 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.92-2.18, 3.21-3.45 (total 8H, m), 3.85 (3H, s), 6.38 (1H, dd, J=2.5 Hz, J=2.45 Hz), 7.88 (1H, d, J=11.3 Hz)

[0650] The compound of Reference Example 147 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 3.29 (4H, t, J=4.8 Hz), 3.84 (4H, t, J=5.1 Hz), 3.87 (3H, s), 6.73 (1H, dd, J=2.8 Hz, J=2.6 Hz), 6.86 (1H, d, J=2.7 Hz), 7.85 (1H, d, J=9.0 Hz)

[0651] The compound of Reference Example 161 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.79-1.02 (9H, m with s at 0.96), 1.59 (2H, t, J=7.8 Hz), 3.86 (3H, s), 3.89 (3H, s), 4.23 (2H, t, J=7.5 Hz), 6.90 (1H, dd, J=8.5 Hz, J=8.5 Hz), 7.03 (1H, s), 7.43 (1H, d, J=1.7 Hz), 7.80 (1H, d, J=8.5 Hz)

[0652] The compound of Reference Example 164 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.85-2.12 (4H, m), 3.12-3.46 (4H, m), 6.35-6.62 (2H, m), 7.74 (1H, d, J=8.6 Hz), 12.35 (1H, brs)

[0653] The compound of Reference Example 165 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 3.25 (4H, t, J=5.0 Hz), 3.70 (4H, t, J=5.0 Hz), 6.80-7.09 (2H, m), 7.75 (1H, d, J=8.7 Hz)

[0654] The compound of Reference Example 180 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.93 (9H, s), 1.55 (2H, t, J=7.5 Hz), 3.76 (3H, s), 4.15 (2H, t, J=7.4 Hz), 7.05 (1H, dd, J=8.6 Hz, J=8.6 Hz), 7.34 (1H, d, J=1.6 Hz), 7.64 (1H, d, J=8.9 Hz), 9.88 (1H, s)

[0655] The compound of Reference Example 148 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.60 (3H, s), 3.85 (3H, s), 5.09 (2H, s), 6.72-6.99 [2H, m, (6.83,1H, s)], 7.25-7.48 (5H, m), 7.93 (1H, d, J=9.1 Hz)

[0656] The compound of Reference Example 150 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35 (6H, d, J=6.1 Hz), 2.59 (3H, s), 3.85 (3H, s), 4.49-4.71 (1H, m), 6.61-6.78 (2H, m), 7.82-7.98 (1H, m)

[0657] The compound of Reference Example 151 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.98 (3H, t, J=7.8 Hz), 1.30-1.89 (4H, m), 2.59 (3H, s), 3.85 (3H, s), 4.13 (2H, t, J=6.5 Hz), 6.68-6.80 (2H, m), 7.83-7.99 (1H, m)

[0658] The compound of Reference Example 152 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03 (6H, d, J=6.7 Hz), 1.98-2.21 (1H, m), 2.59 (3H, s), 3.75 (2H, d, J=6.6 Hz), 3.85 (3H, s), 6.66-6.81 (2H, m), 7.82-7.99 (1H, m)

[0659] The compound of Reference Example 154 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.50 (3H, s), 3.78 (3H, s), 4.75 (2H, s), 6.73-6.93 (2H, m), 7.82 (1H, d, J=8.5 Hz), 13.09 (1H, brs)

[0660] The compound of Reference Example 167 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.26 (6H, d, J=6.0 Hz), 2.49 (3H, s), 4.56-4.80 (1H, m), 6.69-6.85 (2H, m), 7.75-7.85 (1H, m), 12.39 (1H, s)

[0661] The compound of Reference Example 168 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.93 (3H, t, J=7.3 Hz), 1.33-1.55 (2H, m), 1.57-1.81 (2H, m), 2.51 (3H, s), 4.01 (2H, t, J=6.4 Hz), 6.72-6.90 [2H, m, (6.83 (1H, s))], 7.82 (1H, d, J=7.6 Hz), 12.41 (1H, s)

[0662] The compound of Reference Example 169 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.96 (6H, d, J=6.7 Hz), 1.87-2.15 (1H, m),2.50 (3H, s), 3.78 (2H, d, J=6.5 Hz), 6.72-6.88 [2H, m, 6.82 (1H, s)], 7.81 (1H, d, J=7.8 Hz), 12.40 (1H, brs)

Example 1

[0663] 4-Ethoxy-2-methoxybenzoic acid (0.33 g) is dissolved in thionyl chloride (10 ml), and the mixture is refluxed for 30 minutes. The mixture is concentrated under reduced pressure, and thereto is added toluene (20 ml), and the mixture is concentrated again under reduced pressure. The resulting 4-ethoxy-2-methoxybenzoyl chloride is dissolved in dichloromethane (10 ml), and the mixture is cooled at 0° C. over an ice-bath, and thereto is added 7-chloro-5-[N-methyl-N-(2-diethylaminoethyl)amino]carbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepine (0.5 g). To the mixture is added triethylamine (0.6 ml), and the mixture is stirred at the same temperature for two hours. To the reaction solution is added water, and the mixture is extracted with dichloromethane. The extract is dried over sodium carbonate, and purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1˜5:1). The resulting oily product is dissolved in ethanol, and thereto is added conc. hydrochloric acid (0.1 ml), and the mixture is concentrated under reduce pressure to give 7-chloro-5-[N-methyl-N-(2-diethylaminoethyl)amino]carbonylmethyl-1-(2-methoxy-4-ethoxybenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (0.2 g) in a colorless amorphous.

[0664]¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.98-2.06 (13H, m), 2.61-4.88 (21H, m), 6.18-7.45 (6H, m), 10.42-11.52 (1H, m)

Example 2

[0665] To 4-cyclohexylbenzoic acid (2 g) is added thionyl chloride (20 ml), and the mixture is refluxed for two hours. The mixture is evaporated to remove the thionyl chloride to give 4-cyclohexylbenzoyl chloride. To a solution of 5-ethoxycarbonylmethyl-7-chloro-2,3,4,5-tetrahydro-1H-benzazepine (2.2 g) in dichloromethane (50 ml) is added pyridine (3.3 g), and to the mixture is added with stirring the above obtained 4-cyclohexylbenzoyl chloride under ice-cooling, and the mixture is stirred at room temperature overnight. To the reaction solution is added water, and the mixture is extracted with dichloromethane. The extract is washed with diluted hydrochloric acid, and washed with water, and dried over magnesium sulfate. The mixture is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; dichloromethane) to give 5-ethoxycarbonylmethyl-7-chloro-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (4 g) as colorless oil.

[0666]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.27 (3H, t, J=7.1 Hz), 1.20-2.20 (14H, m), 2.30-2.50 (1H, m), 2.60-3.05 (3H, m), 3.10-3.35 (1H, m), 4.10-4.40 (2H, m), 4.45-4.65 (1H, m), 6.57 (1H, d, J=8.4 Hz), 6.96 (1H, d, J=8.1 Hz), 7.00 (2H, d, J=8.0 Hz), 7.10-7.35 (3H, m)

Example 3

[0667] To a solution of 5-ethoxycarbonylmethyl-7-chloro-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (2 g) in ethanol (20 ml) is added a 5N aqueous sodium hydroxide solution (5 ml), and the mixture is stirred at room temperature overnight. The reaction solution is acidified with hydrochloric acid, and the mixture is extracted with dichloromethane. The extract is washed with water, dried over magnesium sulfate, and evaporated to remove the solvent to give 5-carboxymethyl-7-chloro-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (1.8 g) in colorless amorphous.

[0668]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.25 (14H, m), 2.30-2.55 (1H, m), 2.60-3.30 (3H, m), 3.50-3.90 (1H, m), 4.45-4.60 and 5.10-5.30 (1H, m), 6.15 (1H, brs), 6.59 (1H, d, J=8.3 Hz), 6.85-7.00 (3H, m), 7.10-7.35 (3H, m)

[0669] The starting compounds are treated in the same manner as Example 3 to give the compounds of Examples 52, 68, 77, 78, 81-83, 87, 90, 96, 101, 103, 104, 109, 117-118, 120 and 131-135.

Example 4

[0670] To a solution of 5-carboxymethyl-7-chloro-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.7 g) in dichloromethane (50 ml) is added with stirring N,N-bis(2-oxo-3-oxazolidinyl)phosphinic chloride (0.54 g) under ice-cooling, and the mixture is stirred at room temperature for 15 minutes. To the mixture are added with stirring N-methylpiperazine (0.24 ml) and triethylamine (0.46 ml) under ice-cooling, and the mixture is stirred at room temperature overnight. To the reaction solution is added water, and the mixture is extracted with dichloromethane. The extract is washed with water, dried over magnesium sulfate, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=40:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.7 g) as colorless amorphous.

[0671]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-3.40 (22H, m), 2.21 and 2.34 (3H, s), 3.50-3.90 (5H, m), 4.40-4.60 and 5.05-5.20 (1H, m), 6.50-6.60 (1H, m), 6.85-6.95 (1H, m), 7.00-7.15 (3H, m), 7.25-7.50 (2H, m)

[0672] The suitable starting compounds are treated in the same manner as in Example 4 to give the compounds of Examples 7, 9, 11-18, 20-22, 24, 25, 28-36, 38-40, 46-48, 55-67, 70-72, 74-76, 79, 84, 85, 88, 91-94, 98, 121-126, 137 and 138.

Example 5

[0673] 7-Chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)acetyl]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (2.06 g) is dissolved in a mixture of methylene chloride (20 ml) and methanol (20 ml), and thereto is added with stirring sodium borohydride (0.28 g) under cooling over an ice-bath. The mixture is stirred for two hours over an ice-bath, and the mixture is evaporated to remove almost of the solvent. To the residue is added water, and the mixture is extracted with methylene chloride. The organic layer is washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is purified by silica gel column chromatography (solvent; methylene chloride:methanol=20˜10:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)-1-hydroxyethyl]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (2.08 g) as colorless amorphous.

[0674]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-4.0, 4.35-4.65, 4.65-5.0 and 5.0-5.25 (all 27H, m), 6.4-6.65 (1H, m), 6.75-7.6 (10H, m)

[0675] The suitable starting compounds are treated in the same manner as in Example 5 to give the compounds of Examples 22, 46 and 94.

Example 6

[0676] To a mixture of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)-1-hydroxyethyl]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.5 g), acetic acid (5 ml) and acetic anhydride (3 ml) is added a drop of conc. sulfuric acid, and the mixture is stirred at room temperature for 12 hours, and subsequently stirred at a temperature from 60-70° C. for 6 hours. The reaction mixture is poured into ice-water, and thereto is added ethyl acetate (30 ml). The mixture is basified with sodium hydrogen carbonate, and extracted with ethyl acetate. The organic layer is washed successively with a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is purified by silica gel column chromatography (solvent; methylene chloride:methanol=20:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)-1-acetyloxyethyl]-benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.36 g) as colorless amorphous.

[0677]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-4.0, 4.35-4.7 and 4.95-5.25 (all 28H, m), 5.7-6.0 (1H, m), 6.4-6.65 (1H, m), 6.75-7.6 (10H, m)

[0678] The suitable starting compounds are treated in the same manner as in Example 6 to give the compounds of Examples 12 and 48.

[0679] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

Example 7 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 146-148° C. Form: Free Example 8 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/diethyl ether M.p. 184-186° C. Form: Free Example 9 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 1) Form: Free Example 10 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous NMR analysis: 2) Form: Free Example 11 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 3) Form: Free Example 12 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 4) Form: Hydrochloride Example 13 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 186-187° C. Form: Free Example 14 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 162-162.5° C. Form: Free Example 15 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 5) Form: Free Example 16 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 6) Form: Free Example 17 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless needles Solvent for recrystallization: Ethanol M.p. 181-182.5° C. Form: Free Example 18 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless needles Solvent for recrystallization: Ethanol/diethyl ether M.p. 123-126° C. Form: Free Example 19 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless plates Solvent for recrystallization: Dichloromethane/n-hexane M.p. 87.5-88° C. Form: Free Example 20 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 152-153° C. Form: Free Example 21 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 7) Form: Free Example 22 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 8) Form: Free Example 23 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous NMR analysis: 9) Form: Free Example 24 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 79) Form: Free Example 25 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous NMR analysis: 10) Form: Free Example 26 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous NMR analysis: 11) Form: Free Example 27 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless oil NMR analysis: 12) Form: Free Example 28 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 13) Form: Free Example 29 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 14) Form: Hydrochloride Example 30 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 15) Form: Hydrochloride Example 31 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 16) Form: Hydrochloride Example 32 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 17) Form: Hydrochloride Example 33 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH₂ R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 104-108° C. Form: Free Example 34 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 18) Form: Free Example 35 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 19) Form: Free Example 36 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 20) Form: Free Example 37 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless prisms Solvent for recrystallization: Ethyl acetate/diethyl ether/n-hexane M.p. 145-147° C. Form: Free Example 38 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 21) Form: Free Example 39 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 22) Form: Free Example 40 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow viscous oil NMR analysis: 23) Form: Free Example 41 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 133-133.5° C. Form: Free Example 42 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/diethyl ether M.p. 135° C. Form: Free Example 43 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/diethyl ether M.p. 133° C. Form: Free Example 44 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/diethyl ether M.p. 154° C. Form: Free Example 45 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/diethyl ether M.p. 166° C. Form: Free Example 46 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 24) Form: Free Example 47 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 25) Form: Dihydrochloride Example 48 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 26) Form: Free Example 49 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous NMR analysis: 27) Form: Free Example 50 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous NMR analysis: 28) Form: Hydrochloride Example 51 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Yellow plates Solvent for recrystallization: Acetone/diethyl ether M.p. 125° C. Form: Free Example 52 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous NMR analysis: 80) Form: Free Example 53 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White plates Solvent for recrystallization: Ethanol/diethyl ether M.p. 230-232° C. Form: Free Example 54 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless oil NMR analysis: 81) Form: Free Example 55 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 82) Form: Hydrochloride Example 56 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous NMR analysis: 83) Form: Hydrochloride Example 57 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 84) Form: Hydrochloride Example 58 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous NMR analysis: 85) Form: Hydrochloride Example 59 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless viscous oil NMR analysis: 29) Form: Free Example 60 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless viscous oil NMR analysis: 30) Form: Free Example 61 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 31) Form: Hydrochloride Example 62 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 32) Form: Free Example 63 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 33) Form: Free Example 64 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 34) Form: Free Example 65 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 35) Form: Hydrochloride Example 66 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 36) Form: Hydrochloride Example 67 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 174-176° C. Form: Free Example 68 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 203-204° C. Form: Free Example 69 Structure:

X: —CH₂— R¹: 7-Cl R²: —OH R³: H Crystalline form: Colorless amorphous NMR analysis: 37) Form: Free Example 70 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate/n-hexane M.p. 181-182° C. Form: Free Example 71 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 38) Form: Hydrochloride Example 72 Structure:

X: —CH₂— R¹: 7-Cl R²: —OCOCH₂N(CH₃)₂ R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 153-155° C. Form: Hydrochloride Example 73 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous NMR analysis: 39) Form: Free Example 74 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/diethyl ether M.p. 153-154.5° C. Form: Free Example 75 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 160-161° C. Form: Free Example 76 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/diethyl ether NMR analysis: 135-136° C. Form: Free Example 77 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether NMR analysis: 134-136.5° C. Form: Free Example 78 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether NMR analysis: 140.5-142° C. Form: Free Example 79 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane NMR analysis: 199.5-202° C. Form: Free Example 80 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous NMR analysis: 40) Form: Free Example 81 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Dichloromethane/methanol/diethyl ether M.p. 187-190° C. Form: Free Example 82 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Dichloromethane/methanol/diethyl ether M.p. 189-192° C. Form: Free Example 83 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder M.p. 205-207° C. Form: Free Example 84 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 41) Form: Free Example 45 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 42) Form: Free Example 86 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂C₂H₅ R³: H Crystalline form: Colorless oil NMR analysis: 43) Form: Free Example 87 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless oil NMR analysis: 44) Form: Free Example 88 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless oil NMR analysis: 45) Form: Free Example 89 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless oil NMR analysis: 46) Form: Free Example 90 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous NMR analysis: 47) Form: Free Example 91 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Dichloromethane/diethyl ether M.p. 84-88° C. Form: Free Example 92 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 48) Form: Free Example 93 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 49) Form: Free Example 94 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 50) Form: Free Example 95 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate/diethyl ether/n-hexane M.p. 120-122° C. Form: Free Example 96 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous NMR analysis: 51) Form: Free Example 97 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless oil NMR analysis: 52) Form: Free Example 98 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless oil NMR analysis: 53) Form: Free Example 99 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂C₂H₅ R³: H Crystalline form: Colorless oil NMR analysis: 54) Form: Free Example 100 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂C₂H₅ R³: H Crystalline form: Colorless amorphous NMR analysis: 55) Form: Free Example 101 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous NMR analysis: 56) Form: Free Example 102 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 57) Form: Free Example 103 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous NMR analysis: 58) Form: Free Example 104 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous NMR analysis: 59) Form: Free Example 105 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 60) Form: Free Example 106 Structure:

X: —CH₂— R¹: 7-Cl R² and R³: ═O Crystalline form: White powder Recrystallization solvent: Acetone/n-hexane NMR analysis: 61) Form: Free Example 107 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 62) Form: Free Example 108 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 63) Form: Free Example 109 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 169-171° C. Form: Free Example 110 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 64) Form: Free Example 111 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous NMR analysis: 65) Form: Free Example 112 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 139.5-142° C. Form: Free Example 113 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 66) Form: Free Example 114 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 226° C. Form: Free Example 115 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/diethyl ether M.p. 142-142.5° C. Form: Free Example 116 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 67) Form: Free Example 117 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether NMR analysis: 235-237° C. (decomposed) Form: Free Example 118 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether NMR analysis: 183° C. Form: Free Example 119 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane NMR analysis: 68) Form: Free Example 120 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 192° C. Form: Free Example 121 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 69) Form: Free Example 122 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 70) Form: Free Example 123 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 71) Form: Hydrochloride Example 124 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Yellow powder Solvent for recrystallization: Ethanol M.p. 182-184° C. Form: Hydrochloride Example 125 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 72) Form: Hydrochloride Example 126 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 73) Form: Hydrochloride Example 127 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Yellow powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 168° C. Form: Free Example 128 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Dichloromethane/diethyl ether M.p. 186-188° C. Form: Free Example 129 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 120° C. Form: Free Example 130 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 74) Form: Free Example 131 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White needles Solvent for recrystallization: Ethanol/diethyl ether M.p. 109-111° C. Form: Free Example 132 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous NMR analysis: 75) Form: Free Example 133 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Yellow needles Solvent for recrystallization: Methanol/diethyl ether M.p. 202-203° C. Form: Free Example 134 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White needles Solvent for recrystallization: Acetone/n-hexane M.p. 235° C. Form: Free Example 135 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 176° C. Form: Free Example 136 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous NMR analysis: 76) Form: Free Example 137 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous NMR analysis: 77) Form: Free Example 138 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder NMR analysis: 78) Form: Free

[0680] NMR analysis:

[0681] 1) (Example 9) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.78-5.25 (23H, m), 2.96 and 3.20 (all 3H, s), 3.71 (3H, s), 3.83 (3H, s), 6.51-7.18 (6H, m)

[0682] 2) (Example 10) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.25 (14H, m), 2.30-2.55 (1H, m), 2.60-3.30 (3H, m), 3.50-3.90 (1H, m), 4.45-4.60 and 5.10-5.30 (1H, m), 6.15 (1H, brs), 6.59 (1H, d, J=8.3 Hz), 6.85-7.00 (3H, m), 7.10-7.35 (3H, m)

[0683] 3) (Example 11) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-3.40 (22H, m), 2.21 and 2.34 (3H, s), 3.50-3.90 (5H, m), 4.40-4.60 and 5.05-5.20 (1H, m), 6.50-6.60 (1H, m), 6.85-6.95 (1H, m), 7.00-7.15 (3H, m), 7.25-7.50 (2H, m)

[0684] 4) (Example 12) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.82, 1.02 and 1.08 (all 6H, each t, J=7 Hz), 1.2-4.0, 4.35-4.65 and 4.95-5.24 (all 27H, m), 6.35-6.70 (1H, m), 6.75-7.65 (10H, m)

[0685] 5) (Example 15) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.71-2.24 (11H, m), 2.25-5.17 (21H, m), 5.71-7.54 (9H, m)

[0686] 6) (Example 16) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.78-5.16 (32H, m), 5.79-7.51 (10H, m)

[0687] 7) (Example 21) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.00-5.26 (17H, m), 2.28 and 2.34 (each 3H, each s), 6.54-6.75 (1H, m), 6.89-7.93 (8H, m), 8.48-8.74 (1H, m)

[0688] 8) (Example 22) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.85, 1.00 and 1.07 (all 6H, each t, J=7 Hz), 1.1-4.0, 4.35-4.65, 4.65-4.95 and 4.95-5.25 (all 27H, m), 6.4-6.65 (1H, m), 6.75-7.65 (10H, m)

[0689] 9) (Example 23) 1H-NMR (200 MHz, CDCl₃) δ ppm: 2.15 (3H, s), 2.40 (3H, s), 2.71-4.00 (7H, m), 4.01-4.39 (1H, m), 4.69-5.01 (1H, m), 6.42-7.55 (10H, m)

[0690] 10) (Example 25) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.03-2.08 (4H, m), 1.22 (6H, t, J=7.1 Hz), 2.62-4.95 (22H, m), 6.23-7.42 (6H, m), 10.45-11.47 (1H, m)

[0691] 11) (Example 26) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.34-1.72 (1H, m), 1.81-2.25 (3H, m), 2.57-3.18 (3H, m), 3.70 (3H, s), 3.82 (3H, s), 4.35-5.22 (1H, m), 6.53-6.69 (2H, m), 6.73 (1H, dd, J=8.4 Hz, 1.8 Hz), 6.82 (1H, d, J=1.8 Hz), 6.91 (1H, dd, J=8.4 Hz, 2.4 Hz), 7.24 (1H, d, J=2.4 Hz)

[0692] 12) (Example 27) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.32-2.14 (4H, m), 2.57-3.20 (3H, m), 3.52 (3H, s), 3.73 (3H, s), 4.82-5.05 (1H, m), 6.16 (1H, d, J=2.2 Hz), 6.35 (1H, dd, J=8.4 Hz, 2.2 Hz), 6.64 (1H, d, J=8.2 Hz), 6.81 (1H, dd, J=8.4 Hz, 2.4 Hz), 7.06-7.24 (2H, m)

[0693] 13) (Example 28) 1H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.78-2.13 (13H, m), 2.65-5.12 (13H, m), 3.17 and 3.33 (all 3H, s), 3.95 (2H, q, J=6.8 Hz), 6.55-7.58 (7H, m), 10.53-11.48 (1H, m)

[0694] 14) (Example 29) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.98-2.06 (13H, m), 2.61-4.88 (21H, m), 6.18-7.45 (6H, m), 10.42-11.52 (1H, m)

[0695] 15) (Example 30) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.92-1.95 (7H, m), 2.34-4.43 (14H, m), 2.41 and 2.53 (all 3H, s), 2.77 (6H, s), 6.52-7.38 (6H, m), 10.58-11.57 (2H, m)

[0696] 16) (Example 31) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.96-2.03 (4H, m), 2.33-4.62 (13H, m), 2.41 and 2.53 (all 3H, s), 2.76 (3H, s), 3.34 (3H, s), 6.52-7.48 (6H, m), 11.48 (1H, brs)

[0697] 17) (Example 32) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.96-4.87 (22H, m), 2.40 and 2.53 (all 3H, s), 2.73 and 2.77 (all 3H, s), 6.51-7.45 (6H, m), 11.36 (1H, brs)

[0698] 18) (Example 34) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.17-5.24 (22H, m), 6.41-7.58 (12H, m)

[0699] 19) (Example 35) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-5.24 (26H, m), 6.32-7.69 (11H, m)

[0700] 20) (Example 36) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.74-5.24 (32H, m), 6.28-7.70 (11H, m)

[0701] 21) (Example 38)

[0702]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-4.0, 4.35-4.65, 4.65-5.0 and 5.0-5.25 (all 27H, m), 6.4-6.65 (1H, m), 6.75-7.6 (10H, m)

[0703] 22) (Example 39) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-4.0, 4.35-4.7 and 4.95-5.25 (all 28H, m), 5.7-6.0 (1H, m), 6.4-6.65 (1H, m), 6.75-7.6 (10H, m)

[0704] 23) (Example 40) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-4.65 and 4.95-5.25 (all 25H, m), 6.35-6.65 and 6.65-8.2 (all 11H, m)

[0705] 24) (Example 46) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-3.95, 4.45-4.65, 4.7-4.9 and 5.0-5.25 (all 27H, m), 6.4-6.65 and 6.75-7.6 (all 11H, m)

[0706] 25) (Example 47) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.12-2.06 (20H, m), 2.66-4.40 (21H, m), 3.18 and 3.33 (all 3H, s), 6.53-7.41 (7H, m), 10.67-11.53 (2H, m)

[0707] 26) (Example 48) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-3.95, 4.45-4.65 and 4.95-5.25 (all 29H, m), 5.7-6.05 (1H, m), 6.35-6.65 (1H, m), 6.75-7.65 (9H, m)

[0708] 27) (Example 49) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.22-2.34 (4H, m), 2.42-3.42 (3H, m), 2.82 (3H, s), 3.01 (3H, s), 3.68 (3H, s), 4.81-5.41 (1H, m), 5.08 (2H, s), 6.42-7.12 (5H, m), 7.13-7.72 (5H, m)

[0709] 28) (Example 50) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.90-2.25 (4H, m), 1.17 (6H, t, J=7.10 Hz), 2.40-3.90 (17H, m), 4.63-5.17 (1H, m), 4.98 (2H, s), 6.52-7.21 (5H, m), 7.24-7.65 (5H, m), 10.16-10.70 (1H, m)

[0710] 29) (Example 59) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.8-1.2 (6H, m), 1.2-4.0, 4.4-4.65 and 5.0-5.25 (20H, m), 6.45-6.65 (1H, m), 6.6-7.75 (12H, m)

[0711] 30) (Example 60) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.8-1.15 (6H, m), 1.15-3.95, 4.35-4.65 and 4.95-5.25 (all 20H, m, 2.96, 3.17 (each s)), 6.4-7.6 (13H, m)

[0712] 31) (Example 61) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.06-2.41 (7H, m), 2.31 (3H, s), 2.51-4.38 (16H, m), 4.51-4.92 (2H, m), 6.53-7.52 (10H, m), 12.52-12.94 (1H, m)

[0713] 32) (Example 62) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-2.26 (5H, m), 2.02 (3H, s), 2.58-5.29 (7H, m), 3.69 (3H, s), 6.49-7.45 (10H, m)

[0714] 33) (Example 63) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-5.29 (17H, m), 2.16 (3H, s), 2.34 (3H, s), 6.47-7.62 (11H, m)

[0715] 34) (Example 64) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.70-1.19 (6H, m), 1.20-5.25 (20H, m), 2.16 (3H, m), 6.48-7.62 (11H, m)

[0716] 35) (Example 65) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.02-5.28 (23H, m), 2.02 (3H, s), 6.52-7.50 (10H, m), 11.68-12.41 (1H, m)

[0717] 36) (Example 66) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.04-5.32 (29H, m), 2.02 (3H, s), 6.48-7.51 (10H, m), 11.87-12.28 (1H, m)

[0718] 37) (Example 69) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.46-2.41 (4H, m), 2.14 (3H, s), 2.68-2.98 (1H, m), 3.27-3.83 (4H, m), 4.68-5.27 (2H, m), 6.47-7.54 (9H, m), 7.60 (1H, d, J=2.16 Hz)

[0719] 38) (Example 71) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.86-5.20 (32H, m), 6.51-7.52 (10H, m), 11.62-12.24 (1H, m)

[0720] 39) (Example 73) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.28-2.28 (4H, m), 2.14 (3H, s), 2.58-2.92 (2H, m), 2.93-3.28 (1H, m), 3.58 (3H, s), 4.82-5.12 (1H, m), 6.56 (1H, s), 6.65-6.96 (3H, m), 6.97-7.48 (6H, m)

[0721] 40) (Example 80) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.21-2.25 (4H, m), 2.01 (3H, s), 2.26-3.20 (3H, m), 3.59 (3H, s), 4.86-5.22 (1H, m), 6.42-7.45 (10H, m)

[0722] 41) (Example 84) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-4.0, 4.35-4.65 and 5.0-5.25 (all 20H, m, 2.34 (s)), 6.45-6.7 (1H, m), 6.91 (1H, dd, J=2 Hz, 8 Hz), 7.05 (1H, d, J=2 Hz), 7.15-7.7 (9H, m)

[0723] 42) (Example 85) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-3.95, 4.35-4.65, 5.0-5.25 (all 20H, m, 2.33 (s)), 6.4-7.55 [12H, m, 6.59 (d, J=8 Hz), 6.79 (d, J=8.5 Hz)]

[0724] 43) (Example 86) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-2.2 (7H, m), 2.45-3.3, 3.35-3.9, 4.0-4.35, 4.35-4.65 and 4.95-5.35 (all 9H, m, 5.09 (s)), 6.45-6.65 (1H, m), 6.77 (2H, d, J=8.5 Hz), 6.92 (1H, dd, J=2 Hz, 8.5 Hz), 7.05-7.6 (7H, m)

[0725] 44) (Example 87) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.2 (4H, m), 2.5-3.3, 3.35-3.9, 4.3-4.6 and 4.9-5.3 (all 7H, m, 5.06 (s)), 4.45-6.65 (1H, m), 6.74 (2H, d, J=8.5 Hz), 6.93 (1H, dd, J=2 Hz, 8.5 Hz), 7.12 (1H, d, J=2 Hz), 7.12-7.55 (6H, m)

[0726] 45) (Example 88) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.85, 2.85-4.0, 4.35-4.65 and 4.9-5.35 (all 22H, 2.33, 5.10 (each s)), 6.4-6.65 (1H, m), 6.80 (2H, d, J=8.5 Hz), 6.92 (1H, dd, J=2 Hz, 8.5 Hz), 7.04 (1H, d, J=2 Hz), 7.04-7.6 (6H, m)

[0727] 46) (Example 89) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.45 (7H, m, 2.27 (s)), 2.5-3.1, 3.1-3.4, 3.4-3.9, 4.35-4.65 and 5.02-5.30 (all 8H, m, 3.72 (s)),6.56 (1H, d, J=8.3 Hz), 6.92 (1H, dd, J=2.3 Hz, 8.4 Hz), 7.10 (1H, d, J=2.2 Hz), 7.10-7.71 (8H, m)

[0728] 47) (Example 90) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.23-2.47 (4H, m), 2.26 (3H, s), 2.6-3.05 (2H, m), 3.10-3.43, 3.48-3.90, 4.35-4.62 and 5.05-5.29 (all 3H, m), 6.56 (1H, d, J=8.3 Hz), 6.90 (1H, dd, J=2.2 Hz, 8.3 Hz), 7.08 (1H, d, J=2.2 Hz), 7.12-7.55 (6H, m), 7.61 (2H, d, J=8.5 Hz)

[0729] 48) (Example 92) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.84, 1.05 and 1.08 (all 6H, each t, J=7 Hz), 1.2-4.0, 4.1-4.7 and 4.8-5.3 (all 25H, m, 2.24 (s)), 2.61 (q, J=7 Hz), 2.99, 3.19 (each s)), 6.4-7.7 (11H, m, 6.55 (d, J=8 Hz))

[0730] 49) (Example 93) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.90, 0.97 and 1.07 (all 6H, each t, J=7 Hz), 1.15-4.02, 4.38-4.65 and 4.95-5.25 (all 23H, m, 2.26, 3.18 (each s)), 6.54 (1H, d, J=8.3 Hz), 6.77-7.70 (10H, m)

[0731] 50) (Example 94) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.82, 1.00 and 1.07 (all 6H, each t, J=7 Hz), 1.15-3.98, 4.47-4.68, 4.95-5.22 and 5.76-6.10 (all 25H, m), 6.40-6.68 and 6.73-7.68 (all 11H, m)

[0732] 51) (Example 96)

[0733]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-2.4 (4H, m), 2.20 (3H, s), 2.5-3.35, 3.4-3.9, 4.25-4.6 and 4.9-6.2 (all 8H, m, 4.22 (s)), 6.4-6.65 (1H, m), 6.75-6.95 (1H, m), 6.95-7.35 (5H, m), 7.42 (2H, d, J=8.5 Hz), 7.81 (2H, d, J=8.5 Hz)

[0734] 52) (Example 97) 1H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-2.3, 2.5-3.4, 3.5-4.3, 4.35-4.7 and 5.05-5.35 (all 12H, 3.75 (s)), 6.4-6.7 (1H, m), 6.93 (1H, dd, J=2 Hz, 8.5 Hz), 7.13 (1H, d, J=2 Hz), 7.2-7.8 (9H, m)

[0735] 53) (Example 98) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.85,1.03 and 1.08 (all 6H, each t, J=7 Hz), 1.2-4.0, 4.3-4.65 and 4.9-5.3 (all 22H, 2.99, 3.19, 5.10 (each s)), 6.45-7.6 (11H, m)

[0736] 54) (Example 99) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.27 (3H, t, J=7.1 Hz), 1.20-2.20 (14H, m), 2.30-2.50 (1H, m), 2.60-3.05 (3H, m), 3.10-3.35 (1H, m), 4.10-4.40 (2H, m), 4.45-4.65 (1H, m), 6.57 (1H, d, J=8.4 Hz), 6.96 (1H, d, J=8.1 Hz), 7.00 (2H, d, J=8.0 Hz), 7.10-7.35 (3H, m)

[0737] 55) (Example 100) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.08-2.41 (5H, m),1.25 (3H, t, J=7.10 Hz), 2.16 (3H, s), 2.54-5.32 (6H, m), 6.48-7.54 (11H, m)

[0738] 56) (Example 101) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-2.36 (5H, m), 2.26 (3H, s), 2.51-5.35 (4H, m), 6.45-7.50 (11H, m), 8.65-13.90 (1H, m)

[0739] 57) (Example 102)

[0740]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.39 (5H, m), 2.57-3.05 (2H, m), 3.09-5.28 (2H, m), 3.67, 3.72 and 3.82 (each 3H, each s), 6.48-7.81 (10H, m)

[0741] 58) (Example 103) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-2.26 (4H, m), 2.01 (3H, s), 2.52-3.10 (2H, m), 3.01-5.28 (3H, m), 3.61 (3H, s), 6.48-7.88 (10H, m), 8.50-13.9 (1H, m)

[0742] 59) (Example 104) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.32 (4H, m), 2.57-3.09 (2H, m), 3.10-5.29 (3H, m), 3.66 and 3.81 (each 3H, each s), 6.45-7.80 (10H, m), 8.03-13.80 (1H, m)

[0743] 60) (Example 105) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-2.37 (4H, m), 2.14 (3H, s), 2.54-2.97 (2H, m), 2.98-5.20 (3H, m), 3.68 and 3.74 (each 3H, each s), 6.50-7.52 (10H, m)

[0744] 61) (Example 106) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.41-4.06 (5H, m), 2.13 (3H, s), 3.39 (3H, s), 4.36-5.41 (1H, m), 6.49 (1H, s), 6.79 (1H, d, J=8.44 Hz), 6.88 (1H, d, J=7.42 Hz), 7.01-7.62 (6H, m), 7.79 (1H, d, J=2.24 Hz)

[0745] 62) (Example 107) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-2.21 (5H, m), 2.51-3.26 (3H, m), 3.27-4.11 (4H, m), 3.77 (3H, s), 4.36-4.88 (4H, m), 5.71-7.58 (10H, m)

[0746] 63) (Example 108) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.06-2.21 (4H, m), 2.49-5.23 (11H, m), 3.73 (3H, s), 5.78-7.50 (9H, m)

[0747] 64) (Example 110) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.04-2.26 (4H, m), 2.47-5.20 (14H, m), 5.58-7.72 (10H, m)

[0748] 65) (Example 111) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.31-1.69 (1H, m), 1.70-2.24 (3H, m), 2.55-3.20 (3H, m), 4.88-5.20 (1H, m), 5.03 (2H, s), 6.51-7.51 (16H, m)

[0749] 66) (Example 113) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.40 (4H, m), 2.28 (3H, s), 2.60-5.29 (5H, m), 3.74 (3H, s), 6.54-6.78 (1H, m), 6.88-7.06 (1H, m), 7.09-7.46 (6H, m), 7.58-7.79 (1H, m), 8.46-8.66 (1H, m)

[0750] 67) (Example 116) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-2.30 (4H, m), 2.49-5.29 (5H, m), 3.70 (3H, s), 3.87 (2H, s), 6.41-7.75 (12H, m)

[0751] 68) (Example 119) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.21-2.31 (4H, m), 2.60-5.27 (5H, m), 3.75 (3H, s), 6.41-6.63 (1H, m), 6.80-7.53 (2H, m), 7.48 (2H, d, J=8.24 Hz), 7.74 (2H, d, J=8.42 Hz), 9.99-10.02 (1H, m)

[0752] 69) (Example 121) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.16-5.23 (17H, m), 2.35 (3H, s), 6.41-6.62 (1H, m), 6.78-7.53 (2H, m), 7.61 (2H, d, J=8.3 Hz), 7.73 (2H, d, J=8.3 Hz), 9.94 (1H, s)

[0753] 70) (Example 122) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.90-5.24 (26H, m), 6.40-6.61 (1H, m), 6.74-7.82 (6H, m), 9.88-10.01 (1H, m)

[0754] 71) (Example 123) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.94 (3H, t, J=7.3 Hz), 0.78-5.25 (26H, m), 6.48-7.82 (11H, m), 12.35-13.74 (1H, m)

[0755] 72) (Example 125)

[0756]¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.85-5.23 (28H, m), 6.37-7.80 (10H, m), 12.29-13.40 (1H, m)

[0757] 73) (Example 126) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.02-5.22 (27H, m), 6.37-7.76 (11H, m), 12.54-13.50 (1H, m)

[0758] 74) (Example 130)

[0759]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.08-2.37 (4H, m), 2.51-5.45 (11H, m), 3.83 (3H, s), 6.34-7.62 (10H, m)

[0760] 75) (Example 132) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-2.32 (4H, m), 2.12 (3H, s), 2.41-5.30 (7H, m), 6.38-8.08 (11H, m), 8.91-13.00 (1H, m)

[0761] 76) (Example 136) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03-2.36 (4H, m), 2.13 (3H, s), 2.38-5.28 (7H, m), 3.71 (3H, s), 6.41-8.09 (11H, m)

[0762] 77) (Example 137) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-5.10 (25H, m), 6.05-7.50 (15H, m)

[0763] 78) (Example 138) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03-5.08 (20H, m), 2.34 (3H, s), 6.58-7.53 (6H, m), 8.39-9.04 (1H, m)

[0764] 79) (Example 24) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.78-5.25 (23H, m), 2.96 and 3.20 (all 3H, s), 3.71 (3H, s), 3.83 (3H, s), 6.51-7.18 (6H, m)

[0765] 80) (Example 52) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-2.36 (4H, m), 2.20 (3H, s), 2.56-4.00 (4H, m), 4.25-5.41 (1H, m), 6.27-7.76 (11H, m), 10.73-11.74 (1H, m)

[0766] 81) (Example 54) ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.3-1.7 (1H, m), 1.7-2.2 (3H, m), 2.55-3.2 (3H, m), 4.85-5.2 (1H, m), 6.3-7.7 (14H, m)

[0767] 82) (Example 55) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.07-2.04 (10H, m), 2.58-3.98 (18H, m), 4.13-4.36 (1H, m), 4.73 (2H, s), 6.61-7.43 (10H, m), 7.87-8.01 (1H, m), 9.21 (1H, s), 10.32 (1H, brs)

[0768] 83) (Example 56) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.05-2.06 (10H, m), 2.43-3.80 (15H, m), 4.17-4.40 (1H, m), 4.73 (2H, m), 6.63-7.48 (10H, m), 7.84-7.98 (1H, m), 8.56-8.71 (1H, m), 9.22 (1H, s), 10.34 (1H, brs)

[0769] 84) (Example 57) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.08-2.02 (10H, m), 2.62-3.99 (18H, m), 4.12-4.39 (1H, m), 4.82 (2H, s), 6.61-7.57 (9H, m), 7.96-8.11 (1H, m), 9.33 (1H, s), 10.21 (1H, brs)

[0770] 85) (Example 58) ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.04-2.01 (10H, m), 2.43-3.80 (15H, m), 4.13-4.40(1H, m), 4.82 (2H, s), 6.60-7.53 (9H, m), 7.92-8.08 (1H, m), 8.56-8.71 (1H, m), 9.33 (1H, s), 10.35 (1H, brs)

Example 139

[0771] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[2-methoxy-4-{N-[2-(2-methylphenoxy)ethyl]-N-trifluoroacetylamino}benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.45 g) in methanol (20 ml) is added a solution of potassium carbonate (0.11 g) in water (5 ml), and the mixture is stirred at room temperature for 12 hours. The mixture is evaporated to remove the solvent, and thereto is added water. The mixture is extracted with ethyl acetate, and the extract is dried, evaporated to remove the solvent. The resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=80:1→50:1→30:1), and recrystallized from acetone/n-hexane to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{2-methoxy-4-[2-(2-methylphenoxy)ethylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.12 g) as white powder.

[0772] M.p. 160-161° C.

Example 140

[0773] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(2-methoxy-4-trifluoroacetylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.4 g) in dry tetrahydrofuran (20 ml) are added triphenyl-phosphine (0.54 g) and o-(2-hydroxyethoxy)toluene (0.29 g) at room temperature. To the mixture is added dropwise a solution of diethyl azodicarboxylate (0.32 ml) in dry tetrahydrofuran (5 ml), and the mixture is stirred at room temperature for 16 hours. To the mixture is added water, and the mixture is extracted with diethyl ether. The ether layer is dried, evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1→30:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[2-methoxy-4-[N-[2-(2-methylphenoxy)ethyl]-N-trifluoroacetylamino]benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.46 g) as colorless amorphous.

[0774]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-5.10 (25H, m), 6.05-7.50 (15H, m)

[0775] The suitable starting compounds are treated in the same manner as in Example 140 to give the compounds of Examples 13-16, 74-78, 108 and 110.

Example 141

[0776] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(2-methoxy-2-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (2.0 g) in pyridine (30 ml) is added dropwise trifluoroacetic anhydride (1.14 ml) under ice-cooling. To the reaction solution is added a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with ethyl acetate. The extract is washed with water, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1→30:1), and crystallized from acetone/n-hexane to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(2-methoxy-4-trifluoroacetylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (1.86 g) as white powder.

[0777]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03-5.08 (20H, m), 2.34 (3H, s), 6.58-7.53 (6H, m), 8.39-9.04 (1H, m)

[0778] The suitable starting compounds are treated in the same manner as in Example 141 to give the compounds of Examples 7, 8 and 55-58.

Example 142

[0779] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(2-methoxy-2-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.8 g) in methanol (30 ml) are added o-tolualdehyde (0.35 ml) and acetic acid (1 ml), and the mixture is stirred at 50-60° C. for 2-3 hours. To the mixture is added sodium cyanoborohydride (0.11 g) at room temperature, and the mixture is stirred for two hours. The mixture is evaporated to remove the solvent, and to the residue is added water. The mixture is extracted with ethyl acetate, and the extract is dried, and evaporated. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1→25:1), and recrystallized from acetone/diethyl ether to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[2-methoxy-4-(2-methylbenzylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.71 g) as white powder.

[0780] M.p. 153-154.5° C.

[0781] The suitable starting compounds are treated in the same manner as in Example 142 to give the compounds of Examples 13-16, 75-78, 108, 110 and 137.

Example 143

[0782] To a suspension of 7-chloro-5-methoxycarbonylmethyl-1-(2-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (2.6 g) in ethanol (100 ml) are added sodium carbonate (1.5 g), o-xylene dibromide (1.87 g) and sodium iodide (2.42 g), and the mixture is stirred at 60-70° C. for three hours. The mixture is evaporate to remove the solvent, and to the residue is added water, and the mixture is extracted with ethyl acetate. The extract is dried, and evaporate to remove the solvent. The residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=1:10→1:5) to give 7-chloro-5-methoxycarbonylmethyl-1-[2-methoxy-4-(2-isoindolinyl)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.32 g) as colorless amorphous.

[0783]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-2.21 (5H, m), 2.51-3.26 (3H, m), 3.27-4.11 (4H, m), 3.77 (3H, s), 4.36-4.88 (4H, m), 5.71-7.58 (10H, m)

[0784] The suitable starting compounds are treated in the same manner as in Example 143 to give the compounds of Examples 79 and 101.

Example 144

[0785] To a solution of 7-chloro-1-(3-methoxy-4-hydroxybenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.7 g) in dry dimethylformamide (20 ml) are added potassium carbonate (0.35 g) and 2-chlorobenzyl chloride (0.32 ml), and the mixture is stirred at room temperature overnight. To the reaction solution is added water, and the mixture is extracted with ethyl acetate. The extract is washed with water, dried, and evaporated to remove the solvent. The residue is recrystallized from acetone/diethyl ether to give 7-chloro-1-[3-methoxy-4-(2-chlorobenzyloxy)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.76 g) as white powder.

[0786] M.p. 135° C.

[0787] The suitable starting compounds are treated in the same manner as in Example 144 to give the compounds of Examples 24-33, 41, 43-45, 47, 49-51, 86-88 and 98.

Example 145

[0788] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(4-formylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.29 g) in methanol (30 ml) are added o-toluizine (0.2 ml) and acetic acid until the mixture becomes pH 4. The mixture is heated with stirring at 50° C. for 8 hours, and thereto is added sodium cyanoborohydride (0.085 g) with ice-cooling, and the mixture is stirred for one hour. The mixture is evaporated to remove the methanol, and thereto is added water. The mixture is extracted with ethyl acetate, and the extract is washed with water, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=100:1→50:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[4-(2-methylanilinomethyl)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.1 g) as colorless amorphous.

[0789]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-5.24 (26H, m), 6.32-7.69 (11H, m)

[0790] The suitable starting compounds are treated in the same manner as in Example 145 to give the compound of Example 36.

Example 146

[0791] To a solution of 7-chloro-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro -1H-benzazepine (0.7 g) in pyridine (5 ml) is added N,N-dimethylcarbamic chloride (0.42 ml), and the mixture is stirred at 60-70° C. for two hours. The mixture is made acidic with hydrochloric acid, and then extracted with ethyl acetate. The mixture is washed with a saturated aqueous sodium hydrogen carbonate solution, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=1:10→1:1→3:1), and recrystallized from ethanol/diethyl ether to give 7-chloro-1-(3-methoxy-4-dimethylaminocarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.33 g) as white plates.

[0792] M.p. 230-232° C.

[0793] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

Example 147 Structure:

X: —CH₂— R¹: 7-Cl R^(2:) H R³: H Crystalline form: Colorless amorphous Form: Free Example 148 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 149 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder M.p. 194-195° C. Form: Free Example 150 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 151 Structure:

x: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 152 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 153 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 154 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 155 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 156 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 157 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 158 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 159 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 160 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Free Example 161 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 162 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH₂ R³: H Crystalline form: Brown amorphous Form: Free Example 163 Structure:

x: —CH₂— R¹: H R²: H R³: H Crystalline form: Brown amorphous Form: Free Example 164 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 230-232° C. (decomposed) Form: Free Example 165 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Yellow amorphous Form: Free Example 166 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 243-245° C. (decomposed) Form: Free Example 167 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 168 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Pale yellow powder M.p. 203-205° C. (decomposed) Form: Free Example 169 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Brown powder M.p. 178-180° C. Form: Free Example 170 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 202-204° C. (decomposed) Form: Free Example 171 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder M.p. 118-120° C. Form: Free Example 172 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 179-181° C. (decomposed) Form: Free Example 173 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 174 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 175 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 176 Structure:

X: —CH₂— R¹: 7-Cl R²:—CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 177 Structure:

X: —CH₂— R¹: 7-Cl R²:—CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 178 Structure:

X: —CH₂— R¹: 7-Cl R²:—CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 179 Structure:

X: —CH₂— R¹: 7-Cl R²:—CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 180 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 181 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 182 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale yellow oil Form: Free Example 183 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 184 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 185 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 186 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 187 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 188 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 189 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 190 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 191 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder M.p. 130-132° C. Form: Free Example 192 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 193 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 194 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 195 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 196 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 197 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Form: Free Example 198 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 199 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Form: Free Example 200 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 188-190° C. Form: Free Example 201 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 202 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 203 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 204 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 186.5-188° C. Form: Free Example 205 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 206 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Yellow amorphous Form: Hydrochloride Example 207 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 208 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 209 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 210 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 211 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Form: Free Example 212 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless needles Solvent for recrystallization: Ethyl acetate M.p. 204-205° C. Form: Free Example 213 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless prisms Solvent for recrystallization: Ethyl acetate M.p. 157.5-159° C. Form: Free Example 214 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 215 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate M.p. 168.5-169.5° C. Form: Free Example 216 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate M.p. 177-178° C. Form: Free Example 217 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Yellow powder M.p. 195.5-197° C. Form: Free Example 218 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 177-178° C. Form: Free Example 219 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 234-234.5° C. Form: Free Example 220 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Color amorphous Form: Free Example 221 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 143-144.5° C. Form: Free Example 222 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Slightly orange powder Solvent for recrystallization: Acetone/diethyl ether M.p. 231.5-233° C. Form: Free Example 223 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 164-165° C. Form: Free Example 224 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Slightly orange powder Solvent for recrystallization: Ethanol M.p. 175-176.5° C. Form: Free Example 225 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 127.5-128.5° C. Form: Free Example 226 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 176-177° C. Form: Free Example 227 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 104.5-105.5° C. Form: Free Example 228 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 229 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Yellow amorphous Form: Free Example 230 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Form: Free Example 231 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂H R³: H Crystalline form: Yellow amorphous Form: Free Example 232 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Yellow amorphous Form: Free Example 233 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂H R³: H Crystalline form: White powder Form: Free Example 234 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 235 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 236 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Brown powder M.p. 156-159° C. Form: Free Example 237 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 238 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 239 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 240 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochoride Example 241 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 242 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous From: Hydrochloride Example 243 Structure:

X: —CH₂— R¹: 7-Cl R²: —OCH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 244 Structure:

X: —CH₂— R¹: 7-Cl R²: —OCH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 245 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 246 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 247 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 248 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 249 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 84-85.5° C. Form: Free Example 250 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 251 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 252 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 253 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 254 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 255 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Colorless amorphous Form: Free Example 256 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 181.5-182° C. Form: Free Example 257 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 181-182° C. Form: Free Example 258 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 262-265° C. Form: Free Example 259 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 159-160° C. Form: Free Example 260 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Coloreless amorphous Form: Free Example 261 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder solvent for recrystallization: Acetone/n-hexane M.p. 153° C. Form: Free Example 262 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 263 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 264 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 265 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONHCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 266 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH₂ R³: H Crystalline form: Colorless amorphous Form: Free Example 267 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 268 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 269 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH₂ R³: H Crystalline form: Colorless amorphous Form: Free Example 270 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 271 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 272 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Colorless amorphous Form: Free Example 273 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 274 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 275 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 276 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 277 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 278 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 279 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 280 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/n-hexane M.p. 218-221° C. Form: Hydrochloride Example 281 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 214-217° C. Form: Hydrochloride Example 282 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 204-206° C. Form: Hydrochloride Example 283 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONHCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 284 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 285 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 286 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 287 Structure:

X: —CH₂— R¹: H R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Colorless amorphous Form: Free Example 288 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 289 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 290 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Methanol/diethyl ether M.p. 240-242°C. Form: Free Example 291 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 292 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 293 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 294 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 295 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 296 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 297 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 298 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 299 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 300 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 301 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 302 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 303 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 304 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 305 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless prisms Solvent for recrystallization: Acetone/n-hexane M.p. 251-253° C. Form: Free Example 306 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 128-131° C. Form: Free Example 307 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 308 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless prisms Solvent for recrsytallization: Ethanol M.p. 224-225° C. Form: Free Example 309 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 310 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 311 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 312 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 313 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 314 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 315 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Form: Free Example 316 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless prisms Solvent for recrystallization: Acetone/n-hexane M.p. 124-128° C. Form: Free Example 317 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Form: Free Example 318 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 319 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 320 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 321 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 322 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 323 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 324 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 325 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 326 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 327 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 328 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 329 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 330 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 203-204° C. Form: Free Example 331 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 255-258° C. Form: Hydrochloride Example 332 Structure:

X: —CH₂— R¹: H R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Colorless amorphous Form: Free Example 333 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless oil Form: Free Example 334 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 335 Structure:

X: ═CH— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 336 Structure:

X: ═CH— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 337 Structure:

X: ═CH— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Free Example 338 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder M.p. 102-106° C. Form: Free Example 339 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 340 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 341 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 342 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 301 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless needles Solvent for recrystallization: Dichloromethane/ethanol/diethyl ether M.p. 190-193° C. Form: Free Example 344 Structure:

X: —CH₂— R¹: H

R³: H Crystallline form: Coloreless oil Form: Free Example 345 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless viscous oil Form: Free Example 346 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 347 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Dichloromethane/diethyl ether M.p. 180-182° C. ° C. Form: Free Example 348 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Yellow powder Solvent for recrystallization: Ethanol/dichloromethane/diethyl ether M.p. 239-241° C. Form: Free Example 349 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Colorless prisms Solvent for recrystallization: Dichloromethane/ethanol/diethyl ether M.p. 252-254° C. Form: Free Example 350 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless viscous oil Form: Free Example 309 Structure:

X: ═CH— R¹: 7-Cl R²: —CH₂CO₂C₂H₅ R³: H Crystalline form: Pale yellow powder M.p. 71-75° C. Form: Free Example 352 Structure:

X: ═CH— R¹: 7-Cl R²: —CH₂CO₂C₂H₅ R³: H Crystalline form: Pale yellow oil Form: Free Example 353 Structure:

X: ═CH— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Form: Free Example 354 Structure:

X: ═CH— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Form: Free Example 355 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder M.p. 63-69° C. Form: Free Example 356 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Form: Free Example 357 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale yellow powder Form: Free Example 358 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless viscous oil Form: Free Example 359 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless viscous oil Form: Free Example 360 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless viscous oil Form: Free Example 361 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 362 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 363 Structure:

X: —CH₂— R¹: H R² and R³: ═O Crystalline form: Pale yellow amorphous Form: Free Example 364 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Dichloromethane/methanol/diethyl ether M.p. 194-197° C. Form: Free Example 365 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Form: Free Example 366 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 367 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 368 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 134-136° C. Form: Free Example 369 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 97-100° C. Form: Free Example 370 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 371 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 372 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless needles Solvent for recrystallization: Diethyl ether/n-hexane M.p. 135-138° C. Form: Free Example 373 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate M.p. 136-139° C. Form: Free Example 374 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether/ethyl acetate M.p. 143-145° C. Form: Free Example 375 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 376 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether/ethyl acetate M.p. 123-125° C. Form: Free Example 377 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 378 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 164-166° C. Form: Free Example 379 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 380 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOCH₃ R³: H Crystalline form: White powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 168-170° C. Form: Free Example 381 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Dichloromethane/n-hexane M.p. 226-229° C. Form: Free Example 382 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 131-134° C. Form: Free Example 383 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 384 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 133-134.5° C. Form: Free Example 385 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 386 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless viscous oil Form: Free Example 387 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 388 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Free Example 389 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 390 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Free Example 391 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 392 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Free Example 393 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 394 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Free Example 395 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless needles Solvent for recrystallization: Ethyl acetate/n-hexane M.p. 134-135.5° C. Form: Free Example 396 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless needles Solvent for recrystallization: n-Hexane M.p. 108-110.5° C. Form: Free Example 397 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 398 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Color amporphous Form: Free Example 399 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 131-133° C. Form: Free Example 400 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless flakes Solvent for recrystallization: Ethanol M.p. 125-126° C. Form: Free Example 401 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 134-135° C. Form: Free Example 402 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 190-192° C. Form: Free Example 403 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 139-142° C. Form: Free Example 404 Structure:

X: —CH₂— R¹: 7-F

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 405 Structure:

X: —CH₂— R¹: 7-Cl R² and R³: ═O Crystalline form: Pale brown powder M.p. 157-159° C. Form: Free Example 406 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Methanol M.p. 166-167° C. Form: Free Example 407 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 181-182° C. Form: Free Example 408 Structure:

X: —CH₂— R¹: 7-F

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 409 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 108-109° C. Form: Free Example 410 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 104-106° C. Form: Free Example 411 Structure:

X: —CH₂— R¹: H R² and R³: ═O Crystalline form: White powder Solvent for recrystallization: Chloroform/diethy ether M.p. 130-132° C. Form: Free Example 412 Structure:

X: —CH₂— R¹: H R²: —OH R³: H Crystalline form: Pale brown powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 191-193° C. Form: Free Example 413 Structure:

X: —CH₂— R¹: H R²: —OCH₃ R³: H Crystalline form: Colorless viscous oil Form: Free Example 414 Structure:

X: —CH₂— R¹: H R² and R³: ═CH₂ Crystalline form: White powder Solvent for recrystallization: Diethyl ether/n-hexane M.p. 123-124° C. Form: Free Example 415 Structure:

X: —CH₂— R¹: H R²: —OH R³: —CH₂OH Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 416 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 194-197° C. Form: Free Example 417 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale yellow amorphous Form: Hydrochloride Example 418 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 419 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Colorless amorphous Form: Free Example 420 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 421 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale brown amorphous Form: Hydrochloride Example 422 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 423 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless viscous oil Form: Free Example 424 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 425 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Form: Free Example 426 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale brown amorphous Form: Free Example 427 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 223-227° C. Form: Hydrochloride Example 428 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether/n-hexane M.p. 152-154° C. Form: Free Example 429 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 166-168° C. Form: Free Example 430 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 190-192° C. Form: Free Example 431 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 185-187° C. Form: Free Example 432 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale brown powder Solvent for recrystallization: Ehtanol/diethyl ether M.p. 154-158° C. Form: Free Example 433 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale brown amorphous Form: Free Example 434 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 222-225° C. Form: Hydrochloride Example 435 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless prisms Solvent for recrystallization: Ethanol/dichloromethane/diethyl ether M.p. 199-201° C. Form: Free Example 436 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless viscous oil Form: Free Example 437 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 173-175° C. Form: Free Example 438 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 439 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 218-219° C. Form: Free Example 440 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Yellow viscous oil Form: Free Example 441 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Yellow oil Form: Free Example 442 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 143-145° C. Example 443 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Example 444 Structure:

X: —CH₂— R¹: 7-F R²: —OH R³: H Crystalline form: Colorless amorphous From: Free Example 445 Structure:

X: Single bond R¹: 6-Cl

R³: H Crystalline form: Colorless amorphous From: Free Example 446 Structure:

X: Single bond R¹: 6-Cl

R³: H Crystalline form: Colorless amorphous From: Free Example 447 Structure:

X: Single bond R¹: 6-Cl

R³: H Crystalline form: Colorless amorphous From: Free Example 448 Structure:

X: Single bond R¹: 6-Cl

R³: H Crystalline form: Colorless amorphous From: Free Example 449 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONHCH₂CONH₂ R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 208-209° C. Form: Free Example 450 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 451 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Diethy ether M.p. 222-224° C. Form: Free Example 452 Structure:

X: —CH₂— R¹: 7-F R² and R³: ═O Crystalline form: Colorless flake Solvent for recrystallization: Diethyl ether M.p. 97-100° C. Form: Free Example 453 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless prisms Solvent for recrystallization: Diethyl ether M.p. 116-118° C. Form: Free Example 454 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 115-116° C. Form: Free Example 455 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Free Example 456 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Free Example 457 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether/n-hexane M.p. 194-197° C. Form: Free Example 458 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale brown powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 150-154° C. Form: Free Example 459 Structure:

X: Singel bond R¹: H R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 460 Structure:

X: Single bond R¹: H

R³: H Crystalline form: Slightly orange amorphous Form: Dihydrochloride Example 461 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Slightly yellow amorphous Form: Free Example 462 Structure:

X: Single bond R¹: 6-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 463 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 464 Structure:

X: Single bond R¹: 6-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 465 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder M.p. 154-156° C. Form: Free Example 466 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 195-196° C. Form: Free Example 467 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 468 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Example 469 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 470 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorhpus Form: Free Example 471 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 472 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 473 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 474 Structure:

X: —CH₂— R¹: 7-Cl R²: —O(CH₂)₂NHSO₂CH₃ R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 158-159° C. Form: Free Example 475 Structure:

X: —CH₂— R¹: 7-Cl R²: —O(CH₂)₂NHSO₂CH₃ R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 193-194° C. Form: Free Example 476 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 477 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH₂ R³: H Crystalline form: Colorless amorphous Form: Free Example 478 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 479 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Free Example 480 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Free Example 481 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Hydrochloride Example 482 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Hydrochloride Example 483 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 155-158° C. Form: Free Example 484 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 485 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 486 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 487 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 488 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Free Example 489 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Hydrochloride Example 490 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 491 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 492 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 493 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 494 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 495 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 496 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 497 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 498 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 499 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Hydrochloride Example 500 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 501 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 502 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Hydrochloride Example 503 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 504 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Hydrochloride Example 505 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale brown powder Form: Free Example 506 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 209-211° C. Form: Free Example 507 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 169-170° C. Form: Free Example 508 Structure:

X: —CH₂— R¹: 7-Cl R²:—CH₂CONHC₂H₅ R³: H Crystalline form: Colorless amorphous Form: Free Example 509 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 510 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 511 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 512 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 513 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 204-207° C. Form: Hydrochloride Example 514 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/n-hexane M.p. 217-220° C. Form: Hydrochloride Example 515 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Yellow needles Solvent for recrystallization: Water M.p. 198-202° C. Form: Hydroiodide Example 516 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 517 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 518 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 154-155° C. Form: Free Example 519 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 188-190° C. Example 520 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 521 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 522 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 149-151° C. Example 523 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Yellow amorphous Form: Free Example 524 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 525 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 526 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 527 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Brown powder Sovelnt for recrystallization: Diethyl ether M.p. 155-159° C. (decomposed) Form: Hydrochloride Example 528 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Sovelnt for recrystallization: Diethyl ether M.p. 142-145° C. Form: Free Example 529 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 530 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether/n-hexane Form: Free Example 531 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Dihydrochloride Example 532 Structure:

X: —CH₂— R¹: H R²: —CH₂CN R³: H Crystalline form: Colorless amorphous Form: Free Example 533 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Dichloromethane/diethyl ether M.p. 191-194° C. Form: Free Example 534 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Pale brown amorphous Form: Free Example 535 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 536 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 146-147° C. Example 537 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 201-202° C. Form: Free Example 538 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 118-120° C. Form: Free Example 539 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diisopropyl ether M.p. 173-174.5° C. Form: Free Example 540 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 159-161° C. Form: Free Example 541 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 542 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 543 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: n-Hexane M.p. 94-95° C. Form: Free Example 544 Structure:

X: —CH₂— R¹: 7-F

R³: H Crystalline form: Coloreless amorphous Form: Hydrochloride Example 545 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Coloreless amorphous Form: Hydrochloride Example 546 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 174-176° C. Form: Free Example 547 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 548 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 133-135° C. Form: Free Example 549 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 181-184° C. Form: Free Example 550 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Methanol/diethyl ether M.p. 197-200° C. Form: Free Example 551 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate M.p. 162-163.5° C. Form: Free Example 552 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 168-171°C. Form: Free Example 553 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 554 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 555 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 556 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 557 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 150-152° C. Form: Trifluoroacetate Example 558 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Form: Free Example 559 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Diisopropyl ether Form: Free Example 560 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Slightly orange amorphous Form: Hydrochloride Example 561 Structure:

X: —CH₂— R¹: H R²: CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 186-188° C. Form: Free Example 562 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Yellow amorphous Form: Free Example 563 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 564 Structure:

X: —CH₂— R¹: H R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Colorless amorphous Form: Free Example 565 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 566 Structure:

X: —CH₂— R¹: H R²: —CH₂CON(CH₂CH₂OH)₂ R³: H Crystalline form: Colorless amorphous Form: Free Example 567 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 568 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 144-146° C. Form: Free Example 569 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 128-130° C. Form: Free Example 570 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 110-111° C. Form: Free Example 571 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Acetone/diethyl ether M.p. 161.5-163° C. Form: Hydrochloride Example 572 Structure:

X: —CH₂— R¹: H R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Colorless amorphous Form: Free Example 573 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diisopropyl ether M.p. 160-162° C. Form: Free Example 574 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/ethyl acetate/n-hexane M.p. 108-109° C. Form: Free Example 575 Structure:

X: —CH₂— R¹: H R²: —CH₂OH R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 104-106° C. Form: Free Example 576 Structure:

X: —CH₂— R¹: H R²: —CH₂OCOCH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 115-116° C. Form: Free Example 577 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 578 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 579 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 201.5-203° C. Form: Free Example 580 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 196-198° C. Form: Free Example 581 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether/n-hexane M.p. 130-133° C. Form: Free Example 582 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate/n-hexane M.p. 125-127° C. Form: Free Example 583 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 584 Structure:

X: —CH₂— R¹: H R²: —CH₂CONHC₂H₅ R³: H Crystalline form: Colorless amorphous Form: Free Example 585 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 586 Structure:

X: —CH₂— R¹: 7-Cl R²: —OCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 587 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 196-198° C. Form: Free Example 588 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Methanol M.p. 169-170° C. Form: Free Example 589 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Slightly yellow amorphous Form: Free Example 590 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 218-220° C. Form: Free Example 591 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 194-195° C. Form: Free Example 592 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 158-159° C. Form: Free Example 593 Structure:

X: —CH₂— R¹: H R²: —OCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 594 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Form: Free Example 595 Structure:

X: —CH₂— R¹: H R²: —N(C₂H₅)₂ R³: H Crystalline form: Yellow amorphous Form: Free Example 596 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallizatin: Diisopropyl ether M.p. 205-206° C. Form: Free Example 597 Structure:

X: —CH₂— R¹: 7-Cl R²: —OH R³: —CH₂OH Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 142-144° C. Form: Free Example 598 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 132-135° C. Form: Free Example 599 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Pale yellow amorphous Form: Hydrochloride Example 600 Structure:

X: —CH₂— R¹: H R²: —CH₂CONH₂ R³: H Crystalline form: Pale brown powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 119-121° C. Form: Hydrochloride Example 601 Structure:

X: —CH₂— R¹: H R²: —CH₂CONH—OCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 602 Structure:

X: —CH₂— R¹: 7-Cl R²: —OH R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 175-178° C. Form: Free Example 603 Structure:

X: —CH₂— R¹: H R² and R³: ═CH₂ Crystalline form: Pale yellow powder Solvent for recrystallization: Diisopropyl ether/n-hexane M.p. 113-115° C. Form: Free Example 604 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 128-130° C. Form: Free Example 605 Structure:

X: —CH₂— R¹: 7-Cl R²: —O(CH₂)₂NHSO₂CH₃ R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 182-183° C. Form: Free Example 606 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless oil Form: Free Example 607 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless oil Form: Free Example 608 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Yellow amorphous Form: Free Example 609 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Yellow amorphous Form: Free Example 610 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Yellow amorphous Form: Free Example 611 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Brown amorphous Form: Free Example 612 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale brown powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 149-151° C. Form: Free Example 613 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Pale brown amorphous Form: Free Example 614 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Free Example 615 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless oil Form: Free Example 616 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 617 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale brown oil Form: Free Example 618 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale yellow oil Form: Free Example 619 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 620 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 151-161° C. Example 621 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Methanol/diethyl ether M.p. 258-260° C. Form: Hydrochloride Example 622 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 623 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 624 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Coloreless amorphous Form: Free Example 625 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 188-189° C. Form: Free Example 626 Structure:

X: —CH₂— R¹: 7-F R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 627 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 628 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 178-179° C. Form: Free Example 629 Structure:

X: —CH₂— R¹: 7-F R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless oil Form: Free Example 630 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless oil Form: Free Example 631 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder Form: Free Example 632 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 633 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 634 Structure:

X: —CH₂— R¹: 7-F R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 635 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 138-140° C. Form: Free Example 636 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂H R³: H Crystalline form: White powder Solvent for recrystallizatin: Ethanol/diethyl ether M.p. 208-211° C. Form: Free Example 637 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale brown oil Form: Free Example 638 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Pale brown powder Solvent for recrystallization: Chloroform/diethyl ether M.p. 192-194° C. Form: Free Example 639 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 238-239° C. Form: Hydrochloride Example 640 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOCH₃ R³: H Crystalline form: Pale yellow solid Form: Free Example 641 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOCH₃ R³: H Crystalline form: White powder M.p. 82-87° C. Form: Free Example 642 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder M.p. 121-127° C. Form: Free Example 643 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 644 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 645 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: White powder Form: Free Example 646 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 647 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 648 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Brown amorphous Form: Free Example 649 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder Form: Free Example 650 Structure:

X: Single bond R¹: 6-Cl R² and R³: ═O Crystalline form: Slightly yellow powder Form: Free Example 651 Structure:

X: Single bond R¹: 6-Cl R² and R³: ═CH—CO₂C₂H₅ Crystalline form: Slightly yellow amorphous Form: Free Example 652 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂CO₂C₂H₅ R³: H Crystalline form: Slightly yellow amorphous Form: Free Example 653 Structure:

X: Single bond R¹: 6-Cl R² and R³: ═O Crystalline form: Yellow solid Form: Free Example 654 Structure:

X: Single bond R¹: 6-Cl R² and R³: ═O Crystalline form: Yellow powder Form: Free Example 655 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 656 Structure:

X: Single bond R¹: 6-Cl R² and R³: ═CH—COOC₂H₅ Crystalline form: White powder Form: Free Example 657 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 658 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Yellow powder Form: Free Example 659 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 660 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Form: Free Example 661 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Coloreless amorphous Form: Free Example 662 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂COOH R³: H Crystalline form: Coloreless amorphous Form: Free Example 663 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Coloreless amorphous Form: Free Example 664 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Red amorphous Form: Free Example 665 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂COOH R³: H Crystalline form: Yellow amorphous Form: Free Example 666 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 667 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 668 Structure:

X: Single bond R¹: 6-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 669 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 670 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOCH₃ R³: H Crystalline form: Slightly red powder Form: Free Example 671 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: White powder Form: Free Example 672 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Slightly red powder Form: Free Example 673 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 674 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 675 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 676 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 677 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 678 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 679 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 680 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 681 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 183-183.5° C. Form: Free Example 682 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 169.5-170° C. Form: Free Example 683 Structure:

X: —CH₂— R¹: 7-Cl R²: —OCH₂COOCH₃ R³: H Crystalline form: Slightly yellow powder Form: Free Example 684 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 685 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 686 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Slightly yellow powder Form: Free Example 687 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 688 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol/diethyl ether M.p. 176-177° C. Form: Free Example 689 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 690 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Slightly yellow powder Form: Free Example 691 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free

[0794] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

Example 692 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 693 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 694 Structure:

R¹: H R² and R³: ═O Crystalline form: White powder M.p. 166-170° C. Form: Free Example 695 Structure:

R¹: H R² and R³: ═O Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 215-218° C. (decomposed) Form: Free Example 696 Structure:

R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 182-188° C. (decomposed) Form: Free Example 697 Structure:

R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 105-108° C. Form: Free Example 698 Structure:

R¹: H R² and R³: ═O Crystalline form: White powder M.p. 154-158° C. Form: Free Example 699 Structure:

R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 144-145° C. Example 700 Structure:

R¹: H R²: H R³: H Crystalline form: Pale yellow powder Form: Free Example 701 Structure:

R¹: H R² and R³: ═O Crystalline form: Brown powder Form: Free Example 702 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless powder Form: Free Example 703 Structure:

R¹: H R²: H R³: H Crystalline form: Pale yellow oil Form: Free Example 704 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 705 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 706 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 707 Structure:

R¹: H R² and R³: ═O Crystalline form: White powder Form: Free Example 708 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 709 Structure:

R¹: H R² and R³: ═O Crystalline form: White powder Form: Free Example 710 Structure:

R¹: H R² and R³: ═O Crystalline form: Yellow amorphous Form: Free Example 711 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 712 Structure:

R¹: H R² and R³: ═O Crystalline form: White powder Form: Free Example 713 Structure:

R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 714 Structure:

R¹: H R²: H R³: H Crystalline form: Colorless prisms Form: Free Example 715 Structure:

R¹: H R² and R³: ═O Crystalline form: Yellow amorphous Form: Free Example 716 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 717 Structure:

R¹: H R² and R³: ═O Crystalline form: Yellow amorphous Form: Free Example 718 Structure:

R¹: H R² and R³: ═O Crystalline form: White powder Form: Free Example 719 Structure:

R¹: H R² and R³: ═O Crystalline form: Yellow amorphous Form: Free Example 720 Structure:

R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 120-123° C. Form: Free

[0795] The data of NMR analysis of the compounds of the above Examples are as follows.

[0796] NMR analysis:

[0797] The compound of Example 147 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-3.55, 4.50-5.10 [total 16H, m, 2.20 (s), 2.39 (s), 4.69 (s)], 6.54 (1H, d, J=8.27 Hz), 6.71 (1H, d, J=12.82 Hz), 6.78-6.95 (1H, m), 7.05-7.50, 7.75-8.20 (total 3H, m)

[0798] The compound of Example 148 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.98-3.94, 4.41-4.61 and 5.03-5.19 [all 24H, m, 1.12 (t, J=6.67 Hz), 4.57 (s)], 6.38-7.52 and 8.16-8.38 (all 13H, m)

[0799] The compound of Example 150 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.86-3.91, 4.36-4.61 and 5.00-5.20 [all 27H, m, 1.12 (t, J=7.08 Hz), 2.34 (s), 4.54 (s)], 7.39-7.53 and 8.14-8.42 (all 12H, m)

[0800] The compound of Example 151 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.90-4.24, 4.52-4.81 and 5.08-5.24 [all 27H, m, 125 (t, J=7.27 Hz), 2.60 (s), 4.67 (s)], 6.48-7.71 and 8.25-8.62 (all 12H, m)

[0801] The compound of Example 152 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.93-4.18, 4.35-4.69 and 5.00-5.21 [all 27H, m, 1.12 (t, J=6.62 Hz), 2.30 (s), 4.53 (s)], 6.48-7.62 and 8.18-8.40 (all 12H, m)

[0802] The compound of Example 153 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.90-4.18, 4.35-4.70 and 5.05-5.18 [all 27H, m, 3.89 (s)], 6.45-8.12 and 8.90-9.25 (all 12H, m)

[0803] The compound of Example 154 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.95-3.91, 4.31-4.68 and 4.98-5.20 [all 27H, m, 1.12 (t, J=7.20 Hz), 3.80 (s), 4.53 (s)], 6.48-7.61 and 8.29-8.42 (all 12H, m)

[0804] The compound of Example 155 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.96-3.94, 4.40-4.62 and 5.00-5.20 [all 27H, m, 1.12 (t, J=7.18 Hz), 2.33 (s), 4.56 (s)], 6.50-7.60 and 8.34-8.48 (all 12H, m)

[0805] The compound of Example 156 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.96-3.92, 4.31-4.62 and 5.0-5.21 [all 27H, m, 1.12 (t, J=7.24 Hz), 3.77 (s), 4.50 (s)], 6.47-7.65 and 8.32-8.52 (all 12H, m)

[0806] The compound of Example 157 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.84-4.15, 4.39-4.62 and 5.05-5.40 [all 24H, m, 1.11 (t, J=5.70 Hz), 5.15 (s), 5.29 (s)], 6.54 (1H, d, J=6.48 Hz), 6.78 (1H, d, J=6.66 Hz), 6.98-7.75 and 7.95-8.12 [all 11H, m, 7.35 (s), 7.99 (s)]

[0807] The compound of Example 158 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.61 (3H, d, J=5.16 Hz), 0.97 (3H, d, J=5.28 Hz), 1.12-5.15 and 5.76-5.86 [all 15H, m, 2.51 (s), 4.63 (s)], 6.38-8.75 [all 12H, m, 8.47 (s)]

[0808] The compound of Example 159 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-4.20 and 4.31-4.62 [all 21H, m, 4.53 (s), 4.62 (s)], 2.46 (3H, s), 6.35-7.68 and 8.18-8.56 (all 12H, m)

[0809] The compound of Example 160 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.81-4.29, 4.31-4.71 and 4.95-5.13 (all 28H, m), 1.02 (t, J=5.66 Hz), 1.15 (J=5.78 Hz), 4.54 (s), 4.63 (s)], 6.35-7.76 and 8.23-8.69 (all 13H, m, 8.53 (s)]

[0810] The compound of Example 161 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.79-4.72 and 4.90-5.08 [all 22H, m, 2.45 (s), 4.51 (s), 4.61 (s)], 6.30-7.69 and 8.21-8.63 [all 12H, m, 6.38 (d, J=6.80 Hz), 6.50 (d, J=6.66 Hz), 8.53 (s)]

[0811] The compound of Example 162 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.72-4.01, 4.31-4.73 and 4.89-5.18 [all 14H, m, 2.50 (s), 4.52 (s), 4.64 (s), 5.04 (s)], 5.80-7.70 and 8.12-8.58 [all 12H, m, 6.54 (d, J=6.64 Hz), 8.42 (s)]

[0812] The compound of Example 163 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.81-3.59 [all 15H, m, 1.22 (t, J=5.96 Hz), 2.39 (s), 2.98 (q, J=5.94 Hz)], 4.75-5.05 (1H, m), 6.50-7.62 [all 8H, m, 6.60 (d, J=6.20 Hz), 6.85 (t, J=6.10 Hz), 7.01 (t, J=5.96 Hz), 7.56 (s)]

[0813] The compound of Example 165 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.36-1.15, 1.35-3.89 and 4.98-5.09 [all 30H, m, 2.27 (s), 2.29 (s)], 5.65-6.70 (all 11H, m)

[0814] The compound of Example 167 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.92 (6H, d, J=5.36 Hz), 1.35-3.13, 3.28-5-3.58, 3.69-4.01 and 4.82-5.09 [all 14H, m, 2.40 (s), 3.88 (d, J=5.24 Hz)], 6.42-7.40 [all 8H, m, 7.00 (t, J=5.84 Hz)]

[0815] The compound of Example 173 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.01-4.10, 4.41-4.68 and 4.92-5.15 [all 26H, m, 2.33 (s), 2.52 (s), 3.88 (s)], 6.35-7.60 [all 10H, m, 6.59 (d, J=8.35 Hz)]

[0816] The compound of Example 174 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.01-4.12, 4.45-4.70 and 4.92-5.16 [all 26H, m, 2.33 (s), 2.53 (s), 3.88 (s)], 6.41-7.63 (all 11H, m)

[0817] The compound of Example 175 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.52 (3H, d, J=6.52 Hz), 0.96 (3H, d, J=6.59 Hz), 1.05-2.15, 2.21-4.67 and 5.60-5.76 [all 16H, m, 2.59 (s), 3.88 (s)], 6.29-7.62 (all 11H, m)

[0818] The compound of Example 176 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.20, 2.49-4.61 and 5.01-5.28 [all 17H, m, 3.74 (s), 3.77 (s), 4.51 (s)], 6.38-7.60 and 8.21-8.49 [all 12H, m, 6.55 (d, J=8.32 Hz)]

[0819] The compound of Example 177 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.31, 2.51-3.96 and 4.26-5.51 [all 15H, m, 3.77 (s), 4.53 (s)], 6.40-6.69, 6.81-7.00, 7.08-7.51 and 8.25-8.41 (all 12H, m)

[0820] The compound of Example 179 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.21-2.30, 2.55-3.96 and 4.25-5.80 [all 15H, m, 3.76 (s), 4.49 (s)], 6.39-6.65, 6.78-7.51 and 8.25-8.45 [all 12H, m, 6.55 (s), J=8.32 Hz)]

[0821] The compound of Example 180 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-4.65 and 5.05-5.21 [all 18H, m, 2.51 (s), 3.84 (s), 3.88 (s)], 6.40-7.42 [all 10H, m, 6.60 (d, J=7.62 Hz)]

[0822] The compound of Example 181 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-4.36, 4.45-4.83 and 5.0-5.25 [all 18H, m, 2.56 (s), 3.71 (s), 3.81 (s)], 6.43-7.78 [all 11H, m, 6.68 (d, J=7.67 Hz)]

[0823] The compound of Example 182 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.30, 2.45-3.94 and 4.44-4.65 [all 12H, m, 2.52 (s), 3.72 (s)], 6.42-6.77 (1H, m), 6.80-7.55 (6H, m), 8.35-8.75 (2H, m)

[0824] The compound of Example 183 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-4.01, 4.42-4.69 and 5.0-5.21 [all 15H, m, 2.55 (s), 3.81 (s)], 7.49-7.60 (all 11H, m)

[0825] The compound of Example 184 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.06-4.05, 4.39-4.65 and 4.99-5.20 [all 15H, m, 2.50 (s), 3.80 (s)], 6.35-7.52 [all 10H, m, 6.72 (d, J=7.32 Hz)]

[0826] The compound of Example 185 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-3.65, 3.92-4.30 and 4.80-5.10 [all 13H, m, 2.43 (s), 4.10 (s)], 6.46-7.58 and 8.01-8.49 [all 7H, m, 6.62 (d, J=5.48 Hz), 6.74 (d, J=6.66 Hz)]

[0827] The compound of Example 186 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-4.78 and 5.02-5.20 [all 14H, m, 2.44 (s), 4.62 (s)], 6.44-7.15 and 8.19-8.51 [all 12H, m, 6.55 (d, J=8.36 Hz)]

[0828] The compound of Example 187 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-2.30, 2.52-3.31, 3.42-4.78 and 5.09-5.28 [all 17H, m, 3.74 (s), 3.91 (s), 4.61 (s)], 6.42-7.58 and 8.85-9.10 [all 12H, m, 5.80 (d, J=8.36 Hz)]

[0829] The compound of Example 188 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-4.80 and 5.09-5.18 [all 14H, m, 3.88 (s), 4.59 (s)], 5.72-7.60 and 8.87-9.12 [all 13H, m, 6.56 (d, J=8.4 Hz)]

[0830] The compound of Example 189 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.08-4.23, 4.38-4.68 and 5.03-5.19 [all 17H, m, 3.74 (s), 3.79 (s), 4.54 (s)], 6.31-7.80 and 8.10-8.71 (all 12H, m)

[0831] The compound of Example 190 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-3.29, 3.41-4.69 and 5.07-5.27 [all 17H, m, 2.34 (s), 3.74 (s), 4.57 (s)], 6.43-7.71 and 8.21-8.50 [all 12H, m, 6.58 (d, J=6.36Hz), 6.85 (d, J=8.21 Hz)]

[0832] The compound of Example 192 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.09-3.85, 4.01-4.71 and 5.01-5.20 [all 17H, m, 2.46 (s), 3.74 (s), 4.64 (s)], 6.31-7.65 and 8.05-8.41 [all 13H, m, 6.55 (d, J=8.34 Hz)]

[0833] The compound of Example 193 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-4.73 and 5.03-5.26 [all 11H, m, 4.57 (s)], 6.49-7.52 and 8.20-8.41 [all 13H, m, 6.55 (d, J=8.39 Hz)]

[0834] The compound of Example 194 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-3.90, 4.28-4.72 and 5.09-5.26 [all 14H, m, 2.28 (s), 4.51 (s)], 5.60-7.50 and 8.20-8.45 [all 13H, m, 6.55 (d, J=8.58 Hz)]

[0835] The compound of Example 195 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-4.65 and 5.03-5.26 [all 14H, m, 2.33 (s), 4.54 (s)], 6.40-7.51and 8.21-8.43 [all 12H, m, 6.55 (d, J=8.06 Hz)]

[0836] The compound of Example 196 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-2.31, 2.49-4.65 and 5.08-5.26 [all 14H, m, 3.74 (s), 4.57 (s)], 6.45-6.67, 6.80-7.68 and 7.92-8.43 [all 13H, m, 6.57 (d, J=8.22 Hz)]

[0837] The compound of Example 197 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-2.22 and 2.41-5.95 (all 9H, m), 5.14 (2H, s), 6.62-6.48 and 6.75-7.59 [all 13H, m, 6.52 (d, J=8.24 Hz), 7.34 (s)]

[0838] The compound of Example 198 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-4.70 and 5.03-5.25 [all 17H, m, 2.30 (s), 3.74 (s), 4.53 (s)], 6.41-7.65 and 7.91-8.43 [all 13H, m, 6.56 (d, J=8.41 Hz)]

[0839] The compound of Example 199 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.22, 2.48-3.29 and 3.41-4.80 [all 14H, m, 3.67 (s), 3.72 (s)], 5.16 (2H, s), 6.15-6.20, 6.40-6.68, 6.75-8.40 and 9.31-9.48 [all 13H, m, 6.55 (d, J=8.24 Hz), (7.36 (s)]

[0840] The compound of Example 201 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.25 and 2.70-3.25 (all 7.2H, m), 3.45 (2.5H, s), 3.52 (0.5H, s), 3.94 (1.7H, s), 4.03 (0.3H, s), 4.75-5.10 (0.8H, m), 6.75-7.95 (7.2H, m), 8.18 (0.7H, s), 8.40 (0.1H, s)

[0841] The compound of Example 202 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.10-5.0 (28H, m), 6.60-7.80 (11H, m), 10.0-10.5 (1H, m), 11.0-11.8 (1H, m)

[0842] The compound of Example 203 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.25, 2.60-3.15 and 4.85-5.05 (all 8H, m), 2.45 and 2.49 (all 3H, each s), 2.95 and 2.97 (all 6H, each s), 4.53 and 4.65 (all 2H, each s), 6.26-7.55 (11.3H, m), 8.17 (0.7H, s)

[0843] The compound of Example 205 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.20-3.80 and 4.30-4.60 [all 23H, m, 2.34 (s), 2.37 (s)], 4.63 and 4.73 (all 2H, each s), 6.40-7.80 (12H, m), 10.1 and 10.35 (all 1H, each s), 10.7-11.4 (1H, m)

[0844] The compound of Example 206 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.10-4.90 [all 28H, m, 4.64 (s), 4.66 (s), 4.77 (s), 4.86 (s)], 6.65-8.05 (12H, m), 10.4-11.5 (2H, m)

[0845] The compound of Example 207 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.20-2.10 and 2.70-4.90 [all 25H, m, 3.70 (s)], 1.87 (3H, s), 6.50-7.70 (11H, m), 10.1-11.4 (2H, m)

[0846] The compound of Example 208 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.20-2.20, 2.20-3.20, 3.20-4.0 and 4.30-4.50 [all 25H, m, 2.29 (s)], 5.70-6.10, 6.51-7.40 and 7.40-8.00 (all 13H, m)

[0847] The compound of Example 209 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.15, 2.70-3.10 and 4.80-5.00 (all 10H, m), 3.66 and 3.76 [all 2H,each t, J=5.8 Hz], 4.60 and 4.71 [all 2H, each s], 6.70-7.050 (12H, m)

[0848] The compound of Example 210 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.30, 2.70-3.20 and 4.40-5.20 (all 10H, m), 6.25-8.10 (13H, m)

[0849] The compound of Example 211 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.20, 2.70-3.15, 3.20-3.60, 3.90-4.25 and 4.85-5.05 (all 13H, m), 6.21 (0.6H, dd, J=8.4Hz, J=2.2 Hz), 6.50 (0.7H, d, J=1.8Hz), 6.70 (0.9H, d, J=8.4 Hz), 6.80-7.40 (9.8H, m)

[0850] The compound of Example 214 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.20-4.60 [all 20H, m, 2.33 (s)], 5.15 and 5.21 (all 2H, each s), 6.70-8.10 (12H, m)

[0851] The compound of Example 220 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-1.75 (1H, m), 1.85-2.25 (3H, m), 2.75-3.25 (3H, m), 4.58 (2H, d, J=5.6 Hz), 4.9-5.1 (1H, m), 6.3-6.5 (1H, m), 6.58 (1H, d, J=7.4 Hz), 6.87 (1H, t, J=7.6 Hz), 7.06 (1 H, t, J=7.3 Hz), 7.19-7.32 (8H, m), 7.55 (2H, d, J=8.3 Hz)

[0852] The compound of Example 228 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.20, 2.30-3.35, 3.60-3.90 and 4.40-4.70 [all 14H, m, 2.45 (s), 4.48 (s)], 6.45-7.60 (12H, m), 8.28 and 8.49 (all 1H, each s)

[0853] The compound of Example 229 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.30-2.30, 2.70-3.90 and 4.40-4.60 (all 9H, m), 4.62 and 4.64 (all 2H, each s), 6.80-7.65 (12.5H, m), 8.48 and 8.75 (all 0.5H, each s)

[0854] The compound of Example 230 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.30-2.20, 2.70-3.10, 3.20-4.00 and 4.90-5.10 (all 10H, m), 2.44 and 2.48 (all 3H, each s), 4.48 and 4.57 (all 2H, each s), 6.20-7.35 (11H, m), 8.12 and 8.30 (all 1H, each s)

[0855] The compound of Example 231 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.20, 2.65-3.85 and 4.40-4.65 (all 9H, m), 2.42 (3H, s), 3.72 and 3.77 (all 3H, each s), 4.43 and 4.57 (all 2H, each s), 6.40-8.10 (12.2H, m), 8.36 and 8.64 (all 0.8H, each s)

[0856] The compound of Example 232 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-2.2, 2.2-3.35, 3.65-3.75 and 4.40-4.65 (all 9H, m), 2.29 and 2.33 (all 3H, each s), 2.42 (3H, s), 4.44 and 4.57 (all 2H, each s), 6.60-7.60 (13.5H, m), 8.36 and 8.62 (all 0.5H, each s)

[0857] The compound of Example 233 ¹H-NMR (250 MHz, DMSO-d₆) δ ppm: 1.20-2.20, 2.60-3.65 and 4.20-4.40 (all 9H, m), 2.31 (3H, s), 5.10-5.16 (all 2H, each s), 6.46 (0.1H, d, J=8.3 Hz), 6.65 (0.9H, d, J=8.3 Hz), 6.82 (0.9H, d, J=8.4 Hz), 6.98-7.50 (9.4H, m), 9.72, 9.76 and 9.90 (all 0.7H, each s)

[0858] The compound of Example 234 ¹H-NMR (250 MHz, DMSO-d₆) δ ppm: 1.20-1.65,1.80-2.10, 2.65-3.80 and 4.20-4.40 (all 9H, m), 5.11 and 5.18 (all 2H, each s), 6.70-7.80 (11.3H, m), 10.0 and 10.2 (all 0.7H, each s)

[0859] The compound of Example 235 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.20-3.85 and 4.05-4.50 [all 14H, m, 2.18 (s)], 5.50-7.60 (13.2H, m), 7.97 and 8.32 (all 0.8H, each s)

[0860] The compound of Example 237 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.82-4.26, 4.29-4.62 and 4.97-5.22 (all 31H, m), 6.42-8.18 (7H, m)

[0861] The compound of Example 238 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.08-5.25 (31H, m), 6.16-7.80 (9H, m), 12.08-13.75 (1H, m)

[0862] The compound of Example 239 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.91-4.02, 4.43-4.68 and 5.04-5.23 (all 22H, m), 2.31 (3H, s), 6.50-7.74 (11H, m)

[0863] The compound of Example 240 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.51-4.75 [all 28H, m, 2.31 (s), 3.90 (s)],6.46-7.63 (10H, m), 12.01-12.51 (1H, m)

[0864] The compound of Example 241 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.90-5.24 (22H, m), 6.51-7.72 (12H, m)

[0865] The compound of Example 242 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.17-2.55 (10H, m), 2.64-4.91 [all 18H, m, 3.86 (s), 3.90 (s)], 6.79-7.63 (10H, m), 12.42-12.83 (1H, m)

[0866] The compound of Example 243 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.49-2.68 (4H, m), 2.15 (3H, s), 2.69-3.04 and 4.44-5.21 (all 2H, m), 3.66, 3.76, 3.80 and 3.90 (all 6H, each s), 4.04-4.43 (2H, m), 6.54-7.62 (10H, m)

[0867] The compound of Example 244 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.45-2.62 [all 7H, m, 2.13 (s)], 2.71-3.06 and 3.07-5.19 [all 8H, m, 3.65 (s)], 6.00-7.65 (11H, m)

[0868] The compound of Example 245 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.00-5.22 (25H, m), 6.45-7.82 (11H, m, 12.52-13.54 (1H, m)

[0869] The compound of Example 246 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-2.55, 2.56-4.42 and 4.51-4.95 [all 25H, m, 3.95 (s)], 6.76-7.80 (11H, m), 12.40-12.98 (1H, m)

[0870] The compound of Example 247 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.21-5.12 [all 28H, m, 2.15 (s), 2.30 (s)], 6.52-7.72 (10H, m), 12.08-13.78 (1H, m)

[0871] The compound of Example 248 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-5.28 (22H, m), 2.36, 3.45 and 3.52 (each 3H, each s), 6.37-7.82 (9H, m), 12.34-13.35 (1H, m)

[0872] The compound of Example 250 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-4.29 and 4.42-4.68 [all 29H, m, 2.14 (s), 2.30 (s)], 6.47-7.62 (10H, m), 8.49-8.74 (1H, m), 11.17-12.00 (1H, m)

[0873] The compound of Example 251 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-4.22, 4.48-4.73 and 4.92-5.19 [all 32H, m, 3.74 (s), 3.85 (s), 3.93 (s)], 6.70-7.50 (10H, m), 11.62-12.22 (1H, m)

[0874] The compound of Example 252 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.09-2.51, 2.62-4.29 and 4.47-4.88 [all 28H, m, 2.43 (s), 3.94 (s)], 6.69-7.60 (10H, m), 12.06-13.01 (1H, m)

[0875] The compound of Example 253 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.08-4.22, 4.50-4.75 and 4.91-5.10 [all 32H, m, 2.37 (s), 2.42 (s), 3.77 (s)], 6.70-7.60 (10H, m), 11.60-12.50 (1H, m)

[0876] The compound of Example 254 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-2.62 and 2.63-5.19 [all 32H, m, 2.15 (s), 3.91 (s)], 6.51-7.68 (10H, m), 12.00-12.39 (1H, m)

[0877] The compound of Example 255 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.64-4.16 and 4.44-4.68 [all 20H, m, 0.73 (t, J=7.26 Hz), 2.29 (s), 2.55 (s)], 5.60-5.85 and 6.48-7.50 (all 11H, m)

[0878] The compound of Example 260 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.62-1.40, 1.41-2.19, 2.20-4.13 and 4.39-4.69 [all 17H, m, 0.73 (t, J=7.25 Hz), 2.57 (s)], 5.60-5.89 and 6.31-7.73 (all 12H, m)

[0879] The compound of Example 262 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.38-1.82, 1.83-2.35, 2.40-2.58, 2.65-3.78 and 4.82-5.15 [all 14H, m, 2.12 (s), 2.45 (s)], 6.60 (1H, d, J=8.36 Hz), 6.68-6.90 and 6.97-7.48 (all 9H, m)

[0880] The compound of Example 263 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-2.24, 2.37-2.60, 2.64-3.92 and 4.81-5.15 [all 11H, m, 2.48 (s)], 6.61 (1H, d, J=8.38 Hz), 6.71-6.92 and 7.02-7.68 (all 10H, m)

[0881] The compound of Example 264 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.16-4.38, 4.45-4.68 and 4.95-5.18 [all 32H, m, 1.32 (t), 2.12 (s), 2.29 (s), 2.50 (s), 3.30 (s)], 6.40-7.68 (10H, m), 11.48-12.38 (1H, m)

[0882] The compound of Example 265 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.74-4.08 and 4.42-4.69 [all 18H, m, 2.29 (s), 2.54 (s)], 5.59-5.80 and 6.29-7.51 (all 11H, m)

[0883] The compound of Example 266 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-4.05, 4.40-4.66, 4.76-5.09, 5.36-5.81 and 6.30-7.68 [all 25H, m, 2.57 (s), 4.96 (brs)], 6.45 (brs)]

[0884] The compound of Example 267 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.76-2.60 and 2.61-4.92 [all 31H, m, 2.08 (s), 3.85 (s)], 6.30-7.50 (9H, m), 12.22-12.86 (1H, m)

[0885] The compound of Example 268 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.73-2.56 and 2.57-4.94 [all 31H, m, 2.28 (s), 2.39 (s), 3.87 (s)], 6.52-7.52 (9H, m), 12.17-13.00 (1H, m)

[0886] The compound of Example 269 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-4.08, 4.41-4.68, 4.82-5.09, 5.37-5.96 and 6.30-7.58 [all 27H, m, 2.29 (s), 2.54 (s), 5.00 (brs), 6.45 (brs)]

[0887] The compound of Example 270 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-4.29, 4.41-4.68 and 4.96-5.15 [all 29H, m, 2.53 (s), 3.31 (s)], 6.38-7.72 (11H, m), 11.64-12.47 (1H, m)

[0888] The compound of Example 271 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.80-4.98 [23H, m, 2.52 (s), 2.58 (d, J=4.4 Hz)], 6.47-7.72 (11H, m), 12.56-13.30 (1H, m)

[0889] The compound of Example 272 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.58-4.00, 4.12-4.68 and 5.06-5.24 [all 14H, m, 1.63 (s)], 5.45-5.82 and 6.49-8.09 (all 17H, m)

[0890] The compound of Example 273 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.08-5.20 [all 20H, m, 2.85 (s)], 6.48-6.72, 6.81-7.08 and 7.09-7.79 [all 16H, m, 6.74 (d, J=8.2 Hz)], 12.62-13.78 (1H, m)

[0891] The compound of Example 274 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.04-5.24 (22H, m), 6.38-6.71 and 6.72-7.60 (all 16H, m), 12.49-13.31 (1H, m)

[0892] The compound of Example 275 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.10-5.19 [20H, m, 1.74 (s)], 6.41-6.68 and 6.79-7.60 (all 16H, m)

[0893] The compound of Example 276 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.78-2.34, 2.35-4.48, 4.49-4.74 and 4.92-5.12 [all 35H, m, 1.39 (t, d, J=7.0 Hz), 1.83 (s), 3.90 (s), 3.93 (s), 3.95 (s) 3.98 (s)], 6.70-7.60 (9H, m), 11.61-12.24 (1H, m)

[0894] The compound of Example 277 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-2.28, 2.29-4.33, 4.50-4.76 and 4.91-5.13 [all 32H, m, 1.85 (s), 2.39 (s), 2.45 (s), 3.30 (s), 3.77 (s), 3.99 (s)], 6.70-7.58 (10H, m), 11.58-12.27 (1H, m)

[0895] The compound of Example 278 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-4.29 and 4.42-4.93 [all 26H, m, 1.41 (t, J=7.3 Hz), 2.53 (s), 3.87 (s) ], 6.58-7.68 (11H, m), 12.52-13.50 (1H, m)

[0896] The compound of Example 279 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.48-1.41, 1.49-2.88, 2.94-3.28, 3.32-4.80 and 5.31-5.62 [all 22H, m, 0.52 (d, J=6.5 Hz), 0.96 (d, J=6.5 Hz), 2.58 (s), 3.87 (s)], 6.37-6.79 and 6.80-7.75 (all 12H, m)

[0897] The compound of Example 283 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.10-2.96, 2.97-3.91, 4.05-4.61 and 5.05-5.19 [all 20H, m, 1.63 (s), 2.87 (d, J=4.5 Hz)], 5.49-5.78, 6.07-6.32, 6.46-6.69 and 6.81-7.62 (all 9H, m)

[0898] The compound of Example 284 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 0.79-4.32, 4.33-4.66 and 4.99-5.26 [all 34H, m, 1.41 (t, J=5.8 Hz), 3.31 (s)], 6.02-6.37, 6.45-6.68 and 6.78-7.81 (all 8H, m), 11.83-12.39 (1H, m)

[0899] The compound of Example 285 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.17-3.40, 3.52-4.10, 4.11-4.62 and 5.04-5.23 [all 36H, m, 1.41 (t, J=7.18 Hz), 3.31 (s)], 6.05 (1H, t, J=6.68 Hz), 6.51-6.69 and 6.82-7.68 (7H, m), 11.99-12.39 (1H, m)

[0900] The compound of Example 286 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.35-0.65, 0.80-2.12, 2.13-2.88, 2.89-3.23, 3.32-4.24, 4.34-4.65, 5.26-5.47 and 6.31-7.44 [all 38H, m, 0.50 (d, J=6.5 Hz), 0.94 (d, J=6.5 Hz), 2.49 (s)]

[0901] The compound of Example 287 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.50-0.81, 1.00-2.13, 2.14-3.17, 3.21-4.00, 4.36-4.62, 5.48-5.71 and 6.39-7.43 [all 38H, m, 0.65 (t, J=7.3 Hz), 2.49 (s)]

[0902] The compound of Example 288 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.81-2.55 (5H, m), 2.31 (3H, s), 2.56-3.97 4.31-4.70 and 5.08-5.50 (all 4H, m), 6.50-7.83 (12H, m)

[0903] The compound of Example 289 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.49 [all 8H, m, 1.95 (s)], 2.59-3.94, 4.00-4.25, 4.40-4.67 and 5.09-5.29 [all 13H, m, 3.47 (s), 3.55 (s), 3.68 (s)], 6.30-7.48 (9H, m)

[0904] The compound of Example 291 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.27 (5H, m), 2.52-4.33, 4.51-4.73 and 5.00-5.19 [all 13H, m, 3.70 (s), 3.74 (s), 3.75 (s)], 6.71-7.54 (10H, m)

[0905] The compound of Example 292 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.27-2.42 (5H, m), 2.36 (3H, s), 2.58-3.07 (2H, m), 3.10-4.31, 4.38-4.67 and 5.19-5.29 [all 11H, m, 3.53 (s), 3.68 (s)], 6.41-7.48 (9H, m)

[0906] The compound of Example 293 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.09-2.42 (5H, m), 2.58-4.24, 4.49-4.74 and 5.01-5.22 (all 10H, m), 5.24-7.56 (11H, m)

[0907] The compound of Example 294 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.58 (4H, m), 2.35 (3H, s), 2.60-4.09, 4.36-4.68 and 5.02-5.30 (all 5H, m), 3.49 (6H, s), 6.31-7.49 (10H, m)

[0908] The compound of Example 295 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.16-2.47 (4H, m), 2.58-3.40, 3.41-4.38, 4.39-4.68 and 5.09-5.30 (all 11H, m), 3.67 and 3.71 (each 3H, each s), 6.55-7.83 (11H, m)

[0909] The compound of Example 296 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-2.39 (4H, m), 2.51-3.95, 4.36-4.64 and 5.05-5.31 [all 8H, m, 3.65 (s)], 6.50-7.80 (11H, m), 8.99-10.36 (1H, m)

[0910] The compound of Example 297 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.34, 2.58-3.30, 3.31-4.37, 4.51-4.72 and 5.01-5.19 [all 15H, m, 3.76 (s)], 6.71-7.69 (11H, m)

[0911] The compound of Example 298 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.29 (4H, m), 2.57-3.21, 3.30-4.13, 4.49-4.72 and 4.99-5.21 [all 8H, m, 3.73 (s)], 5.41-7.69 (12H, m)

[0912] The compound of Example 299 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-2.22, 2.24-2.52, 2.57-3.19, 3.28-4.41, 4.51-4.73 and 4.99-5.20 [all 18H, m, 2.37 (s), 3.76 (s)], 6.71-7.58 (10H, m)

[0913] The compound of Example 300 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.07-4.14 and 4.15-5.58 [all 16H, m, 2.35 (s), 3.73 (s)], 6.62-7.64 (10H, m)

[0914] The compound of Example 301 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-2.31 [all 10H, m, 1.90 (s)], 2.54-3.23, 3.33-3.97, 4.05-4.31, 4.51-4.71 and 5.01-5.18 [all 11H, m, 3.74 (s)], 6.31-7.50 (9H, m)

[0915] The compound of Example 302 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-2.22 (4H, m), 2.57-3.20, 3.36-4.35, 4.50-4.71 and 5.02-5.20 [all 17H, m, 3.76 (s), 3.91 (s), 3.93 (s)], 6.71-7.55 (9H, m)

[0916] The compound of Example 303 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-2.51 [all 7H, m, 2.39 (s)], 2.57-3.21, 3.22-4.35, 4.51-4.73 and 5.01-5.19 [all 11H, m, 3.76 (s)], 6.70-7.55 (10H, m)

[0917] The compound of Example 304 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.49 [all 10H, m, 2.11 (s), 2.34 (s)], 2.56-3.22, 3.30-4.32, 4.49-4.73 and 5.02-5.19 [all 11H, m, 3.67 (s), 3.74 (s)], 6.48-7.52 (9H, m)

[0918] The compound of Example 307 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.09-2.25 (4H, m), 2.37 and 2.44 (all 3H, each s), 2.55-3.30, 3.31-4.22 and 4.49-6.21 [all 9H, m, 3.73 (s)], 6.70-7.58 (10H, m)

[0919] The compound of Example 309 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-4.23, 4.42-4.69 and 5.03-5.25 [all 18H, m, 2.13 (s), 2.48 (s), 3.71 (s)], 6.30-7.54 (10H, m)

[0920] The compound of Example 310 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.17-2.29 (4H, m), 2.39-4.32, 4.43-4.65 and 5.02-5.22 [all 11H, m, 2.51 (s), 3.74 (s)], 6.41-7.69 (11H, m)

[0921] The compound of Example 311 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-3.99, 4.38-4.65 and 5.01-5.22 [all 15H, m, 2.12 (s), 2.47 (s)], 6.40-7.48 (10H, m)

[0922] The compound of Example 312 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-2.34 (4H, m), 2.35-4.09, 4.40-4.68 and 5.03-5.25 [all 8H, m, 2.50 (s)], 6.40-7.70 (11H, m)

[0923] The compound of Example 313 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-2.52, 2.53-3.94, 3.97-4.32, 4.37-4.62 and 5.07-5.28 [all 20H, m, 3.74 (s)], 6.00-6.32, 6.40-6.68, 6.70-7.01 and 7.02-7.40 (all 8H, m)

[0924] The compound of Example 314 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.08-2.37, 2.38-3.92, 4.01-4.64 and 5.08-5.28 [all 22H, m, 3.74 (s)], 6.07 (1H, t, J=6.7 Hz), 6.41-6.71 and 6.72-7.41 (all 7H, m)

[0925] The compound of Example 315 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.12-2.31, 2.48-3.32, 3.37-3.82, 3.83-4.36, 4.37-4.58 and 5.10-5.25 [all 12H, m, 1.58 (s), 3.59 (s)], 6.43-6.66 and 6.79-7.52 (all 16H, m)

[0926] The compound of Example 316 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.22-3.06, 3.07-3.25, 3.32-3.79, 4.38-4.60 and 5.08-5.24 [all 9H, m, 3.48 (s), 3.58 (s)], 6.42-6.63 and 6.78-8.51 (all 17H, m)

[0927] The compound of Example 317 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.12-2.52, 2.53-3.33, 3.34-3.88, 3.89-4.65, and 5.08-5.25 (all 17H, m), 5.99-6.36, 6.44-6.70 and 6.78-7.55 (all 9H, m)

[0928] The compound of Example 318 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.16-3.32, 3.33-4.62 and 5.08-5.26 (all 19H, m), 6.05 (1H, t, J=6.7 Hz), 6.48-6.74 and 6.75-7.81 (all 8H, m)

[0929] The compound of Example 319 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.19-2.30, 2.57-3.90, 3.91-4.67 and 5.21-5.31 [all 12H, m, 1.59 (s)], 6.49-6.74 and 6.81-7.87 (all 16H, m)

[0930] The compound of Example 320 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.18-2.26 (4H, m), 2.55-3.36, 3.37-3.90, 4.38-4.62 and 5.10-5.30 (all 5H, m), 6.50-6.71 and 6.82-7.81 (all 17H, m)

[0931] The compound of Example 321 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.39, 2.40-4.27, 4.46-4.68 and 5.06-5.22 [all 18H, m, 2.52 (s), 3.72 (s), 3.82 (s) and 3.87 (s)], 6.48-7.68 (11H, m)

[0932] The compound of Example 322 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.86-4.31, 4.43-4.67 and 5.03-5.20 [all 26H, m, 2.43 (s), 2.47 (s), 3.72 (s)], 6.41-7.46 (7H, m)

[0933] The compound of Example 323 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.07-4.31, 4.40-4.67 and 5.02-5.20 [all 28H, m, 2.43 (s), 2.47 (s), 3.72 (s)], 6.40-7.46 (7H, m)

[0934] The compound of Example 324 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-4.31, 4.43-4.65 and 5.02-5.20 [all 24H, m, 2.43 (s), 2.48 (s), 3.71 (s)], 6.44-7.48 (7H, m)

[0935] The compound of Example 325 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.98-5.26 [24H, m, 2.43 (s), 2.48 (s)], 6.42-7.53 [7H, m, 6.64 (d, J=7.3 Hz)]

[0936] The compound of Example 326 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03-4.04, 4.42-4.64 and 5.01-5.21 [all 25H, m, 2.43 (s)], 6.41-7.45 (7H, m)

[0937] The compound of Example 327 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.04-4.01, 4.40-4.66 and 5.02-5.22 [all 21H, m, 2.43 (s), 2.48 (s)], 6.43-7.48 (7H, m)

[0938] The compound of Example 328 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.14-2.28, 2.38-4.02, 4.41-4.68 and 5.02-5.22 [all 15H, m, 2.51 (s), 2.56 (s), 3.78 (s)], 6.48-7.62 (11H, m)

[0939] The compound of Example 329 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.32 (4H, m), 2.43-4.32, 4.45-4.68 and 5.03-5.22 [all 11H, m, 2.55 (s), 2.58 (s), 3.73 (s)], 6.43-7.80 (16H, m)

[0940] The compound of Example 332 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.54-1.04, 1.05-2.25, 2.26-4.18, 4.36-4.74 and 5.52-5.84 [all 17H, m, 0.67 (t, J=7.3 Hz), 2.60 (s)], 6.38-7.82 (17H, m)

[0941] The compound of Example 333 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.9-4.2, 4.4-4.65 and 5.0-5.25 (all 22H, m), 6.45-6.67 and 6.78-7.88 [all 13H, m, 6.58 (d, J=8.3 Hz)]

[0942] The compound of Example 334 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.9-4.1, 4.45-4.65 and 5.0-5.2 [all 22H, m, 1.23 (t, J=7.1 Hz)], 6.35-7.55 (13H, m)

[0943] The compound of Example 335 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.06 (3H, t, J=7.2 Hz), 1.1-1.55 (5H, m), 1.6-2.0 (5H, m), 2.2-2.7 (9H, m), 3.4-3.9 (7H, m), 4.55-4.85 (1H, m), 6.19 (1H, t, J=5.5 Hz), 6.62 (1H, d, J=8.2 Hz), 6.8-7.1 (1H, m), 6.99 (2H, d, J=7.9 Hz), 7.16 (2H, d, J=7.9 Hz), 7.33 (1H, d, J=2.4 Hz)

[0944] The compound of Example 336 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05 (3H, t, J=7.2 Hz), 2.2-2.7 (8H, m), 3.4-3.9 (7H, m), 4.6-4.9 (1H, m), 6.21 (1H, t, J=5.8 Hz), 6.65 (1H, d, J=8.3 Hz), 6.8-7.1 (1H, m), 7.2-7.6 (10H, m)

[0945] The compound of Example 337 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.99 and 1.21 (all 6H, each t, J=7 Hz), 2.0-2.8 (7H, m), 3.0-4.9 (7H, m), 6.34 (1H, t, J=5.5 Hz), 6.65 (1H, d, J=8.1 Hz), 6.75-7.8 (12H, m)

[0946] The compound of Example 339 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-4.2, 4.4-4.7 and 5.0-5.2 (all 19H, m), 6.5-6.7 [1H, m, 6.63 (d, J=7.1 Hz)], 6.8-7.8 (12H, m), 8.2-8.7 (1H, m)

[0947] The compound of Example 340 ¹H-NMR (200 MHz, CDCl₃+DMSO-d₆) δ ppm: 1.0-4.8 and 5.0-5.2 [all 24H, m, 1.47 (t, J=7.1 Hz)], 6.5-8.0 (13H, m), 8.9-9.8 (1H, m), 11.6-12.5 (1H, m)

[0948] The compound of Example 341 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-2.3,2.4-4.7 and 4.9-5.15 (all 21H, m), 6.58 (1H, d, J=7.7 Hz), 6.7-7.8 (12H, m), 8.35-8.8 (1H, m)

[0949] The compound of Example 342 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.9-4.0, 4.4-4.7 and 5.0-5.25 (all 21H, m), 6.5-6.7 (1H, m), 6.8-7.7 (12H, m), 8.2-8.5 (1H, m)

[0950] The compound of Example 344 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.9-4.1, 4.4-4.7 and 4.9-5.15 [all 27H, m, 1.12 (t, J=5.7 Hz), 2.49 (s), 4.52 (s)], 6.4-7.7 [12H, m, 6.62 (d, J=6.1 Hz)], 8.1-8.5 [1H, m, 8.15 (s), 8.41 (s)]

[0951] The compound of Example 345 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 0.9-4.1, 4.3-4.8 and 4.9-5.1 (all 24H, m), 6.7-8.0 (11H, m), 8.3-8.8 [1H, m, 8.38 (s), 8.67 (s)]

[0952] The compound of Example 346 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.0-5.1 [24H, m, 2.46 (s), 2.47 (s), 4.48 (s), 4.61 (s)], 6.35-6.7 [1H, m, 6.58 (d, J=5.5 Hz)], 6.75-8.0 (12H, m), 8.3-8.7 [1H, m, 8.42 (s), 8.59 (s)]

[0953] The compound of Example 350 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-4.2, 4.4-4.7 and 4.9-5.2 [all 23H, m, 2.35 (s), 2.53 (s)], 6.4-8.5 [12H, m, 6.58 (d, J=8.3 Hz), 6.87 (dd, J=8.3, J=2.3 Hz), 6.99 (d, J=2.2 Hz), 7.10 (d, J=8.3 Hz), 10.0-10.04 (1H, m)

[0954] The compound of Example 352 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-1.55 and 1.6-2.0 [all 13H, 1.25 (t, J=7 Hz)], 2.2-2.8 (3H, m), 3.2-3.55 (2H, m), 3.6-3.9 (1H, m), 4.0-4.4 (2H, m), 4.6-4.9 (1H, m), 6.29 (1H, t, J=5.6 Hz), 5.62 (1H, d, J=8 Hz), 6.89 (1H, dd, J=8 Hz, J=2 Hz), 6.99 (2H, d, J=8.2 Hz), 7.18 (2H, d, J=8.2 Hz), 7.35 (1H, d, J=2 Hz)

[0955] The compound of Example 353 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-2.0 (10H, m), 2.2-2.8 (3H, m), 3.2-3.6 (2H, m), 3.65-3.9 (1H, m), 4.6-4.95 (1H, m), 6.28 (1H, t, J=5.4 Hz), 6.61 (1H, d, J=8 Hz), 6.8-7.1 (1H, m), 6.98 (2H, d, J=8 Hz), 7.21 (2H, d, J=8 Hz), 7.35 (1H, d, J=2.3 Hz), 9.03 (1H, brs)

[0956] The compound of Example 354 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.15-2.8 (2H, m), 3.25-3.6 (2H, m), 3.65-3.95 (1H, m), 4.6-4.9 (1H, m), 6.25 (1H, t, J=5.6 Hz), 6.63 (1H, J=8.1 Hz), 6.8-7.0 (1H, m), 7.2-7.6 (10H, m), 9.1 (1H, br)

[0957] The compound of Example 355 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-2.2, 2.6-3.35, 3.4-3.95, 4.0-4.7 and 5.05-5.25 [all 14H, 3.72 (s)], 6.45-6.7 [1H, m, 6.63 (d, J=7.6 Hz)], 6.8-7.5 (12H, m), 8.15-8.4 (1H, m)

[0958] The compound of Example 356 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.2-4.9 and 5.0-5.25 [all 17H, m, 2.46 (s), 3.70 (s), 4.51 (s)], 6.4-7.6 [12H, m, 6.62 (d, J=8.1 Hz)], 8.1-8.6 (1H, m)

[0959] The compound of Example 357 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.1-2.2 (4H, m), 2.6-3.0 (2H, m), 3.1-3.3, 3.4-3.9, 4.4-4.7 and 4.9-5.2 [all 8H, m, 3.73 (s), 4.56 (s)], 6.8-8.0, 8.2-8.4 and 8.45-8.6 (all 12H, m)

[0960] The compound of Example 358 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.1-2.25 (4H, m), 2.5-5.2 (7H, m), 6.2-8.1 (11H, m), 8.3-8.8 [1H, m, 8.42 (s)]

[0961] The compound of Example 359 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-4.7 and 5.0-5.2 [all 15H, m, 2.48 (s), 3.74 (s)], 6.3-6.7 [1H, m, 6.57 (d, J=8.7 Hz)], 6.7-7.8 (10H, m), 8.3-8.8 [1H, m, 8.41 (s), 8.72 (s)]

[0962] The compound of Example 360 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-4.7 and 5.0-5.2 [all 15H, m, 2.49 (s), 3.68 (s)], 6.1-8.0 [10H, m, 6.60 (d, J=8.4 Hz)], 9.4-8.8 [1H, m, 9.54 (s), 9.75 (s)], 12.1-12.4 [1H, m, 12.27 (s)]

[0963] The compound of Example 361 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-3.9 and 4.3-5.3 [all 12H, m, 2.45 (s)], 6.3-6.7 [1H, m, 6.57 (d, J=8.4 Hz)], 6.7-7.8 (10H, m), 8.40 and 8.65 (all 1H, each s)

[0964] The compound of Example 362 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-3.9, 4.2-4.6 and 4.9-5.2 [all 12H, m, 2.43 (s)], 6.3-7.9 [11H, m, 6.57 (d, J=8.3 Hz)], 8.44 and 8.74 (all 1H, each s)

[0965] The compound of Example 363 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.7-2.4 (2H, m), 2.87 (2H, t, J=6 Hz), 3.4-5.2 [4H, m, 4.55 (s)], 6.8-8.1 (12H, m), 8.2-8.7 [1H, m, 8.35 (s)]

[0966] The compound of Example 365 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.1-5.1 [12H, m, 2.42 (s)], 6.4-8.8 [13H, m, 6.72 (d, J=8.4 Hz), 8.60 (d, J=8.3 Hz)], 10.5-10.9 (1H, m)

[0967] The compound of Example 366 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.95-4.05, 4.48-4.72 and 4.96-5.14 [all 27H, m, 1.06 (t, J=7.3 Hz), 2.38 (s)], 6.48-7.73 [12H, m, 6.68 (d, J=7.5 Hz)]

[0968] The compound of Example 367 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05 (3H, t, J=7.3 Hz), 1.18-4.18, 4.42-4.72 and 4.97-5.15 [all 24H, m, 2.34 (s)], 6.40-6.68 and 6.73-7.74 [all 11H, m, 6.61 (d, J=8.3 Hz)]

[0969] The compound of Example 370 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05 (3H, t, J=7.3 Hz), 1.20-2.32, 2.59-4.00, 4.43-4.72 and 5.03-5.21 (all 13H, m), 6.51-7.72 [all 12H, m, 6.69 (d, J=7.4 Hz)]

[0970] The compound of Example 371 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05 (3H, t, J=7.3 Hz), 1.17-2.28, 2.55-3.90, 4.34-4.66 and 5.01-5.22 (all 13H, m), 6.43-7.69 [all 11H, m, 6.63 (d, J=8.3 Hz)]

[0971] The compound of Example 375 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.25 (4H, m), 2.60-3.15 (3H, m), 3.35-3.80 (1H, m), 4.50-5.20 (1H, m), 6.60-6.72 (1H, m), 6.90-7.00 (1H, m), 7.02 (1H, d, J=8.2 Hz), 7.16 (1H, dd, J=2.3 Hz, J=8.3 Hz), 7.21-7.54 (5H, m)

[0972] The compound of Example 377 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-2.28 (4H, m), 2.50-3.18 (3H, m), 3.31-3.60 (1H, m), 4.48-5.19 (1H, m), 7.02 (1H, dd, J=1.7 Hz, J=8.2 Hz), 7.06-7.52 (9H, m)

[0973] The compound of Example 379 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.17-2.30 (4H, m), 2.61-3.20 (2H, m), 3.20-3.45 (1H, m), 3.50-3.98 (1H, m), 4.42-5.33 (1H, m), 6.50-6.65 (1H, m), 6.72-7.56 (6H, m), 7.62 (1H, dd, J=2.0 Hz, J=8.8 Hz), 7.71 (1H, d, J=8.6 Hz), 7.78-8.08 (4H, m), 8.12 (1H, d, J=8.6 Hz)

[0974] The compound of Example 383 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.17-2.22 (7H, m), 2.69-3.93 (6H, m), 4.41-5.23 (1H, m), 6.45-7.73 (11H, m)

[0975] The compound of Example 385 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.28 (7H, m), 2.56-3.08 (4H, m), 3.08-3.96 (2H, m), 4.40-5.21 (1H, m), 6.40-7.16 (4H, m), 7.16-7.75 (8H, m)

[0976] The compound of Example 386 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.70-1.16 (6H, m), 1.20-3.66 (18H, m), 3.66-3.97 (1H, m), 4.48-5.19 (1H, m), 6.51-7.21 (2H, m), 7.21-8.10 (7H, m)

[0977] The compound of Example 387 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.80-1.18 (3H, m), 1.19-2.58 (10H, m), 2.58-3.21 (4H, m), 3.29-3.80 (4H, m), 4.52-5.11 (1H, m), 6.40-6.87 (1H, m), 6.90-7.11 (2H, m), 7.11-7.44 (4H, m), 7.44-7.68 (3H, m)

[0978] The compound of Example 388 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.85 (3H, t, J=7.1 Hz), 1.02 (3H, t, J=7.1 Hz), 1.15-2.28 (3H, m), 2.38 (4H, q, J=7.1 Hz), 2.56 (4H, q, J=7.1 Hz), 2.63-3.49 (4H, m), 3.50-3.79 (1H, m), 4.51-5.14 (1H, m), 5.65-6.79 (2H, m), 6.90-7.10 (2H, m), 7.10-7.21(1H, m), 7.10-7.62 (6H, m)

[0979] The compound of Example 389 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.82-1.19 (3H, m), 1.20-2.55 (10H, m), 2.55-3.19 (4H, m), 3.19-3.87 (4H, m), 4.55-5.13 (1H, m), 6.81-7.72 (10H, m)

[0980] The compound of Example 390 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 0.84 (3H, t, J=7.1 Hz), 1.00 (3H, t, J=7.2 Hz), 1.21-2.42 (8H, m), 2.42-2.68 (4H, m), 2.68-3.46 (3H, m), 3.52-3.81 (1H, m), 4.53-5.14 (1H, m), 5.65-6.51 (1H, m), 6.88-7.11 (2H, m), 7.11-7.22 (1H, m), 7.11-7.65 (8H, m)

[0981] The compound of Example 391 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 0.88-1.27 (3H, m), 1.30-2.89 (10H, m), 2.99-3.20 (1H, m), 3.20-4.12 (7H, m), 4.45-5.29 (1H, m), 6.48-6.67 (1H, m), 6.75-6.90 (1H, m), 7.02 (1H, d, J=2.1 Hz), 7.40-8.09 (7H, m), 8.09-8.20 (2H, m), 8.31 (1H, d, J=8.6 Hz)

[0982] The compound of Example 392 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 0.81-1.19 (6H, m), 1.25-2.30 (4H, m), 2.30-2.77 (7H, m), 2.77-5.30 (6H, m), 6.29-6.78 (2H, m), 6.81 (1H, dd, J=2.2 Hz, J=8.3 Hz), 7.11-7.38 (1H, m), 7.38-7.66 (3H, m), 7.66-7.89 (2H, m), 7.89-8.24 (4H, m), 8.31 (1H, d, J=8.6 Hz)

[0983] The compound of Example 393 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 0.78-2.30 (5H, m), 2.35 (3H, s), 2.41-2.60 (3H, m), 2.60-3.52 (3H, m), 3.52-4.01 (5H, m), 4.46-5.26 (1H, m), 6.50-6.09 (1H, m), 6.89 (1H, dd, J=2.2 Hz, J=8.3 Hz), 7.02 (1H, d, J=2.2 Hz), 7.09-7.20 (1H, m), 7.28-7.55 (1H, m), 7.60-7.90 (6H, m), 8.38 (1H, s)

[0984] The compound of Example 394 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 0.79-1.20 (6H, m), 1.29-2.82 (10H, m), 2.82-4.02 [9H, m, 3.00 (s), 3.22 (s)], 4.40-5.25 (1H, m), 6.50-6.68 (1H, m), 6.83-7.20 (3H, m), 7.25-7.52 (1H, m), 7.58-7.87 (6H, m), 8.37 (1H, d, J=5.2 Hz)

[0985] The compound of Example 397 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-4.18, 4.40-4.72 and 4.96-5.20 [all 25H, m, 2.35 (s), 2.88 (q, J=7.4 Hz)], 6.40-7.85 (11H, m)

[0986] The compound of Example 398 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-4.10, 4.49-4.75 and 4.98-5.18 [all 25H, m, 2.33 (s)], 6.45-7.72 (12H, m)

[0987] The compound of Example 404 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.28 (10H, m), 2.54-4.08 (15H, m), 4.18-5.22 (1H, m), 6.50-6.70 (2H, m), 6.72-6.90 (1H, m), 7.08-7.78 (9H, m) 12.02 (1H, brs)

[0988] The compound of Example 408 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-5.15 (17H, m), 2.86 (3H, s), 6.49-6.70 (2H, m), 6.72-6.90 (1H, m), 6.93-7.81 (9H, m), 12.27 (1H, brs)

[0989] The compound of Example 413 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.46-4.00, 4.27-4.80 and 5.03-5.17 (all 13H, m), 6.68 (1H, d, J=8.3 Hz), 6.80-7.69 (12H, m)

[0990] The compound of Example 415 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-4.15 and 4.80-5.10 (all 13H, m), 6.45-7.90 (12H, m)

[0991] The compound of Example 417 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.87 (3H, t, J=7.3 Hz), 1.35-2.22, 2.66-3.17 and 4.88-5.09 (all 10H, m), 4.08 (2H, t, J=7.3 Hz), 6.57 (1H, d, J=8.3 Hz), 6.89 (1H, dd, J=2 Hz, J=8.3 Hz), 7.15-7.49 (3H, m), 7.53-7.69 (2H, m), 11.39-11.64 (1H, brs)

[0992] The compound of Example 418 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.99-4.17 and 4.45-4.65 [all 25H, m, 1.84 (s)], 6.56-6.65, 6.82-7.02 and 7.11-7.58 (all 6H, m), 7.75-7.96 (1H, m), 8.50-8.66 (1H, m), 8.71-8.93 (1H, m)

[0993] The compound of Example 419 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.64-0.85, 1.10-4.00, 4.40-4.70 and 5.58-5.72 (all 17H, m), 6.36-7.62 (8H, m), 7.75-7.96 (1H, m), 8.49-8.70 (1H, m), 8.70-7.95 (1H, m)

[0994] The compound of Example 420 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-4.2, 4.45-4.6 [all 20H, m, 2.04 (s), 2.34 (s)], 5.15 and 5.22 (all 2H, each s), 6.8-7.8 (all 12H, m)

[0995] The compound of Example 421 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.40-1.85, 1.85-2.14, 2.68-3.10 and 4.85-5.06 (all 8H, m), 2.53 and 2.59 (all 3H, each s), 6.60 (1H, d, J=8.3 Hz), 6.85 (1H, dd, J=2.9 Hz, J=8.3 Hz), 6.96 (1H, d, J=7.9 Hz), 7.12-7.22 (2H, m), 7.29, 7.40 and 7.58 (all 2H, each s), 7.89-8.09 (1H, m), 8.43-8.66 (1H, m), 8.69-8.86 (1H, m), 8.90-9.11 (1H, m)

[0996] The compound of Example 422 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-2.10, 2.32-2.90, 3.20-3.45 and 4.70-4.90 (all 8H, m), 6.42 (1H, d, J=6.8 Hz), 6.71 (1H, dd, J=2.0 Hz, J=6.8 Hz), 6.85 (1H, d, J=2.0 Hz), 7.00-7.65 (10H, m)

[0997] The compound of Example 423 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.36-1.73, 1.84-2.25, 2.65-3.16 and 4.93-5.16 (all 8H, m), 6.61 (1H, d, J=8.3 Hz), 6.90 (1H, dd, J=2 Hz, J=8.3 Hz), 7.08-7.70 (10H, m)

[0998] The compound of Example 424 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-4.00 and 4.45-4.65 [all 23H, m, 1.62, 2.34 (s), 2.54 (s)], 6.55-6.65, 6.82-7.01 and 7.10-7.56 (all 6H, m), 7.74-7.93 (1H, m), 8.50-8.67 (1H, m), 8.74-8.90 (1H, m)

[0999] The compound of Example 425 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.38-2.22, 2.65-3.15 and 4.95-5.12 (all 8H, m), 6.61 (1H, d, J=8.4 Hz), 6.80-7.00 (2H, m), 7.20-7.38 (4H, m), 7.62 (1H, d, J=9.1 Hz), 7.98 (2H, d, J=8.3 Hz), 8.09 (1H, d, J=6.9 Hz)

[1000] The compound of Example 426 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 0.90-1.90, 1.90-2.23, 2.46-2.70 and 4.67-4.90 (all 8H, m), 8.44 (1H, d, J=8.4 Hz), 6.75 (1H, dd, J=2.4 Hz, J=8.4 Hz), 6.92 (1H, d, J=2.4 Hz), 7.05-7.75 and 7.96-8.04 (all 6H, m), 8.30-8.45, 8.53-8.74 and 8.80-8.87 (all 2H, m)

[1001] The compound of Example 433 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.22-3.13, 3.44-3.73 and 4.71-4.93 (all 8H, m), 6.80 (1H, dd, J=2.5 Hz, J=8.5 Hz), 6.96-7.85 (9H, m), 8.63-8.76 (1H, m)

[1002] The compound of Example 436 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-4.2, 4.4-4.7 and 5.0-5.2 [all 16H, m, 2.34 (s)], 6.5-6.75 (1H, m), 6.8-7.8 [all 11H, m, 7.50 (d, J=6.7 Hz), 7.70 (d, J=5.7 Hz)]

[1003] The compound of Example 438 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.22-3.95, 4.43-4.62 and 5.03-5.24 [all 30H, m), 2.34 (s)], 6.56 and 6.63 (all 1H, each d, J=8.3 Hz), 6.89-7.32 (4H, m), 7.37-7.55 (2H, m)

[1004] The compound of Example 440 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.84-4.00 and 4.39-4.60 (all 22H, m), 6.23-6.39 (2H, m), 6.50-6.66 (1H, m), 6.82-6.99 (1H, m), 6.99-7.15 (3H, m), 7.15-7.36 (2H, m), 7.42-7.62 (2H, m)

[1005] The compound of Example 441 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.80-4.00 and 4.38-4.65 [all 32H, m, 1.92 (s), 3.23 (s)], 5.85 and 5.87 (all 2H, each s), 6.57 (1H, d, J=8.5 Hz), 6.80-7.20 (4H, m), 7.45-7.65 (2H, m)

[1006] The compound of Example 444 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.57-2.34 (4H, m), 2.51-2.90 (2H, m), 4.74-5.23 (2H, m), 6.53-6.76 (2H, m), 6.91-7.62 (9H, m)

[1007] The compound of Example 445 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.75-2.0, 2.2-3.10 and 3.45-4.10 (all 18H, m), 4.65 (2H, s), 6.66-7.70 [all 11H, m, 6.67 (d, J=8.6 Hz)], 7.59 (d, J=8.5 Hz), 8.80 (1H, s)

[1008] The compound of Example 446 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.8-2.0 and 2.25-2.50 (all 6H, m), 2.31 (3H, s), 2.60 (1H, dd, J=15.7 Hz, J=8.3 Hz), 2.80 (1H, dd, J=15.7 Hz, J=5.7 Hz), 3.45-3.60 (3H, m), 3.60-3.80 (2H, m), 3.89 (2H, t, J=6.6 Hz), 4.60 (2H, s), 6.67 (1H, d, J=8.7 Hz), 6.88 (1H, dd, J=8.7 Hz, J=2.2 Hz), 7.00-7.50 (8H, m), 7.56 (2H, d, J=8.6 Hz), 8.41 (1 H, s)

[1009] The compound of Example 447 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.65-2.0 and 2.1-2.55 [all 12H, m, 2.32 (s), 2.35 (s)], 2.60 (1H, dd, J=15.7 Hz, J=8.2 Hz), 2.80 (1H, dd, J=15.7 Hz, J=5.8 Hz), 3.48-3.52 and 3.67-3.72 (all 5H, m), 3.89 (2H, t, J=6.6 Hz), 4.59 (2H, s), 6.67 (1H, d, J=8.6 Hz), 6.78 (2H, d, J=8 Hz), 6.87 (2H, d, J=8.6 Hz), 7.20 (2H, d, J=8 Hz), 7.37 (2H, d, J=8.6 Hz), 7.55 (2H, d, J=8.6 Hz), 8.37 (1H, s)

[1010] The compound of Example 448 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.70-2.10, 2.20-2.90 and 3.50-4.0 [all 21H, m, 2.23 (s), 2.31 (s)], 4.71 (2H, s), 6.68 (1H, d, J=8.6 Hz), 6.85-7.03, 7.15-7.43 and 7.60-7.67 (all 11H, m), 9.57 (1H, s)

[1011] The compound of Example 450 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.96-4.70 (29H, m), 1.45 (3H, t, J=7.0 Hz), 4.07 (2H, q, J=7.0 Hz), 5.58-7.36 (7H, m)

[1012] The compound of Example 455 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.95-4.00, 4.42-4.63 and 5.04-5.18 (all 22H, m), 6.46-6.67 (1H, m), 6.79-6.95 (1H, m), 6.95-7.25 (4H, m), 7.32-7.51 (2H, m), 7.52-7.75 (2H, m)

[1013] The compound of Example 456 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.95-3.93, 4.41-4.62 and 5.01-5.20 [all 25H, m, 2.24 (s)], 6.45-6.62 (1H, m), 6.72-6.95 (2H, m), 6.95-7.08 (1H, m), 7.10-7.45 (3H, m), 7.45-7.69 (2H, m)

[1014] The compound of Example 459 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.42 (6H, t, J=7.2 Hz), 1.75-2.05 (1H, m), 2.15-2.40 (1H, m), 2.40-3.90 (11H, m), 3.94 (2H, t, J=6.5 Hz), 6.73-7.15 (3H, m), 7.25-7.60 (10H, m), 8.35-8.75 (1H, m), 11.3-11.7 (1H, m)

[1015] The compound of Example 460 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.24 (3H, t, J=7 Hz), 1.4-1.5, 1.85-3.30, 3.40-4.20 and 4.65-4.85 (all 15H, m), 3.72 (2H, q, J=7 Hz), 6.8-7.7 (13H, m), 12.6-12.9 (1H, m)

[1016] The compound of Example 461 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03 (6H, t, J=7 Hz), 1.75-2.0 (1H, m), 2.10-2.30 (1H, m), 2.35-2.90 (8H, m), 3.35-3.80(3H, m), 3.90 (2H, t, J=6.6 Hz), 6.72 (1H, d, J=8.6 Hz), 6.8-7.0 (2H, m), 7.23 (1H, d, J=2.2 Hz), 7.35-7.66 (9H, m)

[1017] The compound of Example 462 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03 (3H, t, J=7.2 Hz), 1.75-2.0 (1H, m), 2.15-2.40 (1H, m), 2.40-2.90 (8H, m), 3.50-3.60 (3H, m), 3.65-3.85 (2H, m), 3.93 (2H, m), 6.75-7.0 and 7.2-7.65 (all 12H, m)

[1018] The compound of Example 463 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-1.70,1.70-3.0, 3.0-3.6, 3.6-3.8 and 3.8-4.0 (all 32H, m), 6.73 (1H, d, J=8.6 Hz), 6.87 (1H, dd, J=8.6 Hz, J=2.4 Hz), 7.13 (2H, d, J=8 Hz), 7.23 (1H, d, J=2.4 Hz), 7.33 (2H, d, J=8 Hz), 8.4-8.7 (1H, m), 11.2-11.6 (1H, m)

[1019] The compound of Example 464 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10 (3H, t, J=7.2 Hz), 1.2-1.65, 1.7-2.0, 2.1-2.9, 3.4-3.6, 3.6-3.8 and 3.8-4.0 (all 28H, m), 6.77 (1H, d, J=8.7 Hz) 6.90 (1H, dd, J=8.7 Hz, J=2.3 Hz), 7.13 (2H, d, J=8.2 Hz), 7.19 (1H, d, J=2.3 Hz), 7.31 (2H, d, J=8.2 Hz)

[1020] The compound of Example 467 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 1.10-2.10, 2.55-4.05, 4.45-4.61 and 4.68-4.71 (all 41H, m), 6.94-7.38 (3H, m), 12.00-12.27 (1H, brs)

[1021] The compound of Example 469 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.24 (5H, m), 2.63-3.31 (3H, m), 3.70 and 3.75 (all 3H, s), 4.08-5.20 (1H, m), 6.46-6.62 (1H, m), 6.36-7.00 (1H, m), 7.10-7.48 (3H, m), 8.43-8.56 (2H, m)

[1022] The compound of Example 470 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-5.08 (26H, m), 6.15-7.53 (16H, m)

[1023] The compound of Example 471 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.97-2.20, 2.20-4.06 and 4.40-4.63 [all 36H, m), 1.41 (t, J=7.2 Hz), 1.71 (s), 3.31 (s)], 6.59 (1H, d, J=8.5 Hz), 6.84-7.60 (6H, m), 12.7-13.4 (1H, brs)

[1024] The compound of Example 472 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-226, 2.50-4.10, 4.40-4.60 and 5.00-5.15 (all 29H, m), 6.58 (1H, d, J=8.2 Hz), 6.65-7.48 (6H, m), 12.12 (1H, brs)

[1025] The compound of Example 473 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.30-2.20, 2.50-4.10, 4.38-4.60 and 4.98-5.16 (all 29H, m), 6.50-7.20 (5H, m), 7.36 (2H, d, J=8.6 Hz), 12.15 (1H, brs)

[1026] The compound of Example 476 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.16-4.10 and 4.30-4.53 (all 35H, m), 6.47-6.80, 6.80-7.65 and 7.86-8.10 (all 7H, m), 15.51-15.98 (1H, br)

[1027] The compound of Example 477 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-2.11 (4H, m), 2.45-3.78 (5H, m), 4.23-5.10 (1H, m), 6.61-7.75 (14H, m)

[1028] The compound of Example 478 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.62 (1.5H, d, J=6.5 Hz), 0.99 (1.5H, d, J=6.5 Hz), 1.03-5.74 (14H, m), 6.43-7.80 (11H, m)

[1029] The compound of Example 479 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.80-3.90, 4.41-4.64 an 5.05-5.70 (all 35H, m), 6.49-6.63 (1H, m), 6.71-7.20 (4H, m), 7.20-7.50 (2H, m)

[1030] The compound of Example 480 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.92-2.25, 2.38-3.27, 3.27-4.00, 4.50-4.60 and 4.85-5.02 (all 29H, m), 6.62-7.45 (6H, m)

[1031] The compound of Example 481 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.82-4.17, 4.36-4.60 and 5.07-5.13 [all 26H, m, 2.99 (s), 3.23 (s)], 6.40-6.66 (1H, m), 6.75-7.78 (8H, m), 7.84 (1H, d, J=3.7 Hz)

[1032] The compound of Example 482 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.77-1.14, 1.14-2.24, 2.24-4.04, 4.33-4.53 and 4.97-5.13 [all 27H, m, 2.89 (s), 3.14 (s)], 6.42-6.61 (1H, m), 6.77-7.10 (2H, m), 7.28-7.80, 7.80-8.12 [all 6H, m, 7.88 (s)]

[1033] The compound of Example 484 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-5.33 (22H, m), 6.49-7.32 (12H, m), 11.92-12.70 (1H, m)

[1034] The compound of Example 485 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-5.28 (20H, m), 1.38 (3H, t, J=7.2 Hz), 3.32 (3H, s), 6.61 (1H, d, J=8.3 Hz), 6.91 (1H, dd, J=8.3 Hz, J=2.2 Hz), 7.03 (1H, d, J=2.2 Hz), 7.18-7.76 (9H, m), 11.94 (1H, brs)

[1035] The compound of Example 486 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-5.13 (24H, m),1.35 (3H, t, J=7.3 Hz), 1.45 (3H, t, J=7.0 Hz), 4.08 (2H, q, J=7.0 Hz), 6.18-7.46 (6H, m), 11.59-12.58 (1H, m)

[1036] The compound of Example 487 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.93-3.98 (26H, m), 4.51-5.15 (1H, m), 4.97 and 5.10 (all 2H, s), 6.23-7.51 (11H, m)

[1037] The compound of Example 488 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.90-2.12, 2.12-2.40, 2.40-3.63 and 4.45-4.84 (all 38H, m), 6.98-7.35 (2H, m), 7.38-7.44 (1H, m)

[1038] The compound of Example 489 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.06-5.19 (36H, m), 6.16-7.49 (6H, m), 11.28-11.99 (1H, m)

[1039] The compound of Example 490 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.32-4.57 (22H, m), 1.45 (3H, t, J=7.0 Hz), 2.58 and 2.60 (all 3H, s), 4.08 (2H, q, J=7.0 Hz), 6.43-6.63 (2H, m), 7.05-7.44 (4H, m), 12.15 (1H, brs)

[1040] The compound of Example 491 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-5.21 (31H, m), 6.11-7.61 (6H, m), 8.54-8.72 (1H, m), 11.27-12.03 (1H, m)

[1041] The compound of Example 492 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.23-5.03 (25H, m), 1.46 (3H, t, J=7.0 Hz), 4.08 (2H, q, J=7.0 Hz), 6.16-7.44 (6H, m), 12.47 (1H, brs)

[1042] The compound of Example 493 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-4.67 (29H, m), 4.97, 5.10 (all 2H, s), 6.22-7.51 (11H, m), 11.43-12.04 (1H, m)

[1043] The compound of Example 494 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.21-4.62 (26H, m), 4.98 and 5.11 (all 2H, s), 6.22-7.51 (11H, m), 8.55-8.71 (1H, m), 11.39-11.81 (1H, m)

[1044] The compound of Example 495 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.21-4.90 (22H, m), 1.34 (3H, t, J=7.3 Hz), 4.98 and 5.11 (all 2H, s), 6.27-7.53 (11H, m), 12.48 (1H, brs)

[1045] The compound of Example 496 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.83-3.98 (24H, m), 2.99 and 3.15 (all 3H, s), 3.62 and 3.86 (all 3H, s), 4.49-5.19 (1H, m), 4.97 and 5.10 (all 2H, s), 6.23-7.53 (11H, m)

[1046] The compound of Example 497 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.20, 2.60-4.55 (all 26H, m), 6.45-6.55 (1H, m), 6.80-6.95 (1H, m), 6.95-7.60 (4H, m), 7.90-8.08 (1H, m), 11.86 (1H, brs)

[1047] The compound of Example 498 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.20, 2.55-3.40, 3.40-4.10, 4.35-4.53 and 4.96-5.20 (all 26H, m), 6.53 (1H, d, J=8 Hz), 6.91 (1H, dd, J=0.2 Hz, J=8 Hz), 7.04 (1H, d, J=0.2 Hz), 7.13 (2H, d, J=8.6 Hz), 7.40 (2H, d, J=8.6 Hz), 12.15 (1H, s)

[1048] The compound of Example 499 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.20, 2.20-3.45, 3.45-4.10 and 4.45-4.65 (all 29H, m), 6.50-6.62, 6.75-7.55 and 7.95-8.07 (all 7H, m), 11.8-12.2 (1H, m)

[1049] The compound of Example 500 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.25-3.40, 3.40-4.15 and 4.40-4.60 (all 29H, m), 6.50-6.62, 6.80-7.45 and 7.85-7.95 (all 7H, m), 12.06 (1H, brs)

[1050] The compound of Example 501 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-4.10, 4.45-4.60 and 5.00-5.20 (all 29H, m), 6.56 (1H, d, J=6.4 Hz), 6.80-7.50 (5H, m), 7.96 (1H, d, J=8.2 Hz), 12.01 (1H, brs)

[1051] The compound of Example 502 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-4.18 and 4.50-4.70 (all 29H, m), 6.60-6.90, 6.90-7.51, 7.51-7.66 and 8.15-8.22 (all 7H, m), 11.8-12.25 (1H, br)

[1052] The compound of Example 503 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.78-3.95, 4.42-4.60 and 5.05-5.21 (all 26H, m), 6.49-6.62 (1H, m), 6.82-6.98 (1H, m), 6.98-7.52 (6H, m)

[1053] The compound of Example 504 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.16-4.06, 4.43-4.64 and 4.92-5.10 (all 26H, m), 6.72-7.65 (7H, m), 11.87-12.18 (1H, br)

[1054] The compound of Example 505 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.00-3.95, 4.20-4.44 and 4.90-5.05 (all 22H, m), 5.10-6.50 (1H, br), 6.65-6.76 (1H, m), 6.90-7.05 (1H, m), 7.20-7.35 (1H, m), 7.35-7.50 (2H, m), 7.70-7.85 (2H, m)

[1055] The compound of Example 508 ¹H-NMR (250 MHz, CDCl₃) δ ppm: 0.65-0.82, 1.00-2.17, 2.17-2.95, 2.95-3.51, 3.55-3.90, 4.18-4.35, 4.42-4.63, 5.03-5.18 and 5.50-5.75 (all 25H, m), 6.51-6.68 (1H, m), 6.85-7.45 (5H, m), 7.51-7.65 (1H, m)

[1056] The compound of Example 509 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.49 (3H, d, J=6.3 Hz), 0.95 (3H, d, J=6.3 Hz), 1.1-4.2 [all 16H, m, 3.02 (s)], 6.55-6.80 (3H, m), 7.15-7.45 (5H, m)

[1057] The compound of Example 510 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.0-2.2, 2.4-4.0 and 4.5-4.6 [all 25H, m, 2.87 (s), 3.0 (s)], 6.1-7.5 [all 7H, m, 6.26 (dd, J=8.8 Hz, J=2.5 Hz)]

[1058] The compound of Example 511 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-5.35 [24H, m, 2.33 (s)], 6.75-8.26 (7H, m)

[1059] The compound of Example 512 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-1.5, 1.5-4.0, 4.4-4.7 and 4.9-5.1 (all 28H, m, 2.02 (s), 2.18 (s)), 6.13-7.70 (7H, m)

[1060] The compound of Example 516 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.30-1.85, 1.85-2.22, 2.61-3.16 and, 4.82-5.06 (8H, m), 2.50 and 2.56 (all 3H, each s), 6.55-6.65, 6.78-6.95 and 7.10-7.60 (all 8H, m), 8.52-8.70 (2H, m)

[1061] The compound of Example 517 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.30-2.30, 2.30-3.15, 3.36-3.60 and 4.98-5.08 [all 11H, m, 2.49 (s), 2.54 (s)], 6.60 (1H, d, J=8.4 Hz), 6.75-6.95 (2H, m), 6.95-7.10 (1H, m), 7.10-7.51 (5H, m), 8.38-8.87 (2H, m)

[1062] The compound of Example 520 ¹H-NMR (200 MHz, CDCl₃) δ ppm: [all 6H, m, 0.651 (d, J=6.5 Hz), 1.02 (d, J=6.5 Hz), 1.15 (d, J=6.5 Hz, 1.22 (d, J=6.5 Hz)], 1.25-2.22, 2.45-2.90, 3.00-3.21, 3.50-4.00 and 4.44-4.67 [all 13H, m, 2.57 (s), 2.63 (s)], 6.50-7.96 and 8.65-8.95 (11H, m)

[1063] The compound of Example 521 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-4.9 [all 26H, m, 3.06 (s)], 6.65-7.75 (all 7H, m), 12.4-13.2 (1H, m)

[1064] The compound of Example 523 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.20, 2.29-3.12, 3.29-3.61 and 4.81-5.10 [all 21H, m, 2.34 (s)], 6.23 (1H, dd, J=8.72 Hz, J=8.73 Hz), 6.50 (1H, d, J=2.48 Hz), 6.56-7.49 (5H, m)

[1065] The compound of Example 524 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.89 (6H, d, J=6.54 Hz), 1.32-2.20, 2.30-3.31, 3.42-3.95 and 4.82-5.12 (all 19H, m), 6.39-7.49 (7H, m)

[1066] The compound of Example 525 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-2.20 and 2.20-4.90 (all 23H, m), 6.35-6.69, 6.69-7.00, 7.00-8.34 and 8.65-9.16 (all 10H, m), 1.65-12.8 (1H, br)

[1067] The compound of Example 526 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.64, 0.98,1.16 and 1.19 (all 6H, each d, J=6.5 Hz), 1.20-1.49, 1.49-2.23, 2.23-4.60 and 4.95-5.12 [all 13H, m, 2.58 (s), 2.65 (s)], 6.05-6.50, 6.50-6.65, 6.70-6.95, 7.05-7.45, 7.45-7.90, 7.90-8.33 and 8.75-9.15 (all 12H, m)

[1068] The compound of Example 529 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-4.88 (20H, m), 1.19 and 1.35 (all 9H, s), 2.46, 2.49 and 2.51 (all 6H, s), 6.58-7.47 (7H, m), 12.76 (1H, brs)

[1069] The compound of Example 530 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.25, 2.36-3.60 and 4.47-5.09 [all 11H, m, 2.52 (s), 2.58 (s)], 6.60-6.75 (1H, m), 6.75-7.09 (8H, m), 8.52-8.75 (2H, m)

[1070] The compound of Example 531 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.05-2.0, 2.5-4.0 and 4.2-4.6 (all 24H, m), 6.14-7.5 [all 7H, m, 6.16 (d, J=8.8 Hz)], 11.1-11.5 (2H, m)

[1071] The compound of Example 532 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.3-2.4, 2.7-4.1, 4.5-4.7 and 5.0-5.2 (all 9H, m), 6.7-7.8 (12H, m)

[1072] The compound of Example 534 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.30-2.25, 2.40-3.50 and 4.86-5.08 [all 11H, m, 2.53 (s), 2.58 (s)], 6.00-7.60 and 8.55-8.85 (all 10H, m)

[1073] The compound of Example 535 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-4.90 (23H, m), 6.50-6.66, 6.80-7.68 and 8.60-8.91 (all 9H, m), 12.77-13.45 (1H, br)

[1074] The compound of Example 541 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.00-2.11, 2.12-3.90 and 4.18-4.71 [all 34H, m, 2.32 (s), 2.36 (s)], 6.40-7.55 (6H, m), 9.82-10.16 and 10.80-11.24 (all 1H, m)

[1075] The compound of Example 542 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.15, 2.6-3.15, 3.65-4.0, 4.47, 4.57 and 4.85-5.0 [all 16H, m, 4.47 (s), 4.57 (s)], 6.48 and 6.7-7.45 [all 12H, m, 6.48 (s)]

[1076] The compound of Example 544 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.16-4.92 (20H, m), 2.53 and 2.59 (all 3H, s), 6.54-6.75 (1H, m), 6.91-7.18 (2H, m), 7.23-7.68 (8H, m), 12.83 (1H, brs)

[1077] The compound of Example 545 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.17-5.20 (20H, m), 4.93 and 5.11 (all 2H, s), 6.53-7.56 (12H, m), 12.34-13.15 (1H, m)

[1078] The compound of Example 547 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.82-5.25 (27H, m), 3.87 (2H, t, J=6.4 Hz), 6.53-6.80 (2H, m), 6.83-7.68 (6H, m), 12.32-13.22 (1H, m)

[1079] The compound of Example 553 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-4.21, 4.49-4.71 and 4.98-5.20 (all 25H, m), 6.28-7.61 (11H, m)

[1080] The compound of Example 554 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-4.04, 4.48-4.71 and 4.97-5.19 [all 26H, m, 2.17 (s), 2.21 (s)], 6.42-7.74 (12H, m)

[1081] The compound of Example 555 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.57 (4H, t, J=5.10 Hz), 3.32 (4H, t, J=5.10 Hz), 3.56 (2H, s), 3.86 (3H, s), 6.74 (1H, dd, J=8.94 Hz, J=8.96 Hz), 6.85 (1H, d, J=2.55 Hz), 7.25-7.45 (5H, m), 7.83 (1H, d, J=8.91 Hz)

[1082] The compound of Example 556 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03-2.22, 2.60-3.15, 3.90-4.28 and 4.80-5.00 [all 28H, m, 1.45 (s), 3.98 (d, J=6.31 Hz)], 6.68-7.42 and 7.58-7.71 (all 7H, m)

[1083] The compound of Example 558 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.9-2.2, 2.6-3.2 and 4.5-4.9 [all 15H, m, 4.51 (s), 4.58 (s)], 6.8-7.15, 7.15-7.40 and 7.40-7.90 (all 12.2H, m), 8.47 and 8.7 (all 0.8H, each s)

[1084] The compound of Example 559 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.80-4.08 and 4.42-4.69 [all 29H, m, 2.40 (s)], 6.58-7.78 [all 8H, m, 7.51 (d, J-.2.01 Hz)]

[1085] The compound of Example 560 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.0-1.25, 1.25-2.25, 2.5-3.7 and 4.4-5.0 (all 15H, m), 6.73-7.75 (all 10H, m), 8.53 (2H, d, J=5 Hz)

[1086] The compound of Example 562 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.17-4.86 (26H, m), 6.50-7.65 (10H, m), 12.67 (1H, brs)

[1087] The compound of Example 563 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.96-2.35 and 2.36-4.97 (all 20H, m), 6.79-8.06 (12H, m), 10.02-10.46 and 11.00-11.60 (all 1H, m)

[1088] The compound of Example 564 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.52-2.22, 2.23-4.24, 4.34-4.71 and 4.91-5.17 [all 14H, m, 0.66 (t, J=7.3 Hz)], 5.53-5.74 and 6.29-6.58 (all 1H, m), 6.89-7.88 (12H, m)

[1089] The compound of Example 565 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.08-2.21, 2.23-4.08 and 4.21-5.11 [all 26H, m, 2.31 (s), 2.44 (s)], 6.46-7.78 (11H, m), 10.00-10.28 and 10.96-11.45 (all 1H, m)

[1090] The compound of Example 566 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.16-2.20, 2.28-4.10, 4.42-4.71 and 4.89-5.11 [all 25H, m, 2.42 (s), 2.56 (s)], 6.59-7.68 (11H, m)

[1091] The compound of Example 567 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.79-2.19, 2.29-3.80 and 3.96-4.67 (all 23H, m), 6.52-7.48 and 7.49-8.45 (11H, m), 9.83-10.21 and 10.86-11.51 (all 1H, each br)

[1092] The compound of Example 572 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.57-0.90, 1.03-2.22, 2.27-4.69 and 5.49-5.71 [all 20H, m, 0.67 (t, J=7.3 Hz), 2.44 (s), 2.59 (s)], 5.49-5.71 and 6.36-7.65 (all 12H, m)

[1093] The compound of Example 577 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.3-2.2, 2.65-3.2, 4.0-4.4 and 4.8-5.0 (all 11H, m), 6.18 (1H, dd, J=8.4 Hz, J=2.4 Hz), 6.48 (1H, d, J=2.2 Hz), 6.69 (1H, d, J=8.4 Hz), 6.85-7.45 (9H, m)

[1094] The compound of Example 578 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-2.2, 2.5-3.4, 4.15-4.4 and 4.7-5.1 (all 14H, m), 6.15 (0.88H, d, J=8 Hz), 6.43 (0.94H, s), 6.67 (1.07H, d, J=8 Hz), 6.8-7.5 (9.1H, m)

[1095] The compound of Example 583 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.95-4.9 [all 26H, m, 1.10 (t, J=7.2 Hz), 2.47 (d, J=4 Hz)], 6.8-7.2, 7.2-7.55, 7.55-8.25 and 8.25-8.60 [all 14H, m, 8.44 (s)]

[1096] The compound of Example 584 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.666 (3H, t, J=7.3 Hz), 1.50-4.00 (17H, m), 6.40-7.20 (13H, m)

[1097] The compound of Example 585 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.00-4.20 and 4.40-4.35 [all 23H, m, 2.50 (s), 2.54 (s)], 6.80-7.65 (12H, m)

[1098] The compound of Example 586 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.45-3.13, 3.20-4.00 and 4.20-5.18 (all 13H, m), 6.62-7.66 (12H, m)

[1099] The compound of Example 589 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.8-3.7 and 4.85-5.15 [all 24H, m, 2.37 (s)], 5.9-7.2 [all 7H, m, 6.27 (s)]

[1100] The compound of Example 593 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.3-3.8, 4.2-4.8 and 4.9-5.15 [all 12H, m, 3.36 (s), 3.48 (s), 4.55 (s)], 6.6-7.95 (12H, m), 8.15-8.7 (1H, m)

[1101] The compound of Example 594 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-2.35, 2.60-3.15, 3.75-4.20, 4.30-4.61 and 4.79-5.11 (all 12H, m), 6.71-7.75 (7H, m)

[1102] The compound of Example 595 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-3.30, 3.30-4.18 and 4.40-4.62 (all 20H, m), 6.55-6.72 (1H, m), 6.72-6.97 (2H, m), 6.97-7.18 (2H, m), 7.18-7.67 (7H, m)

[1103] The compound of Example 599 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-1.58, 1.58-4.29 and 4.50-4.85 [all 25H, m, 1.71 (s), 2.54 (s)], 7.05-7.72 (12H, m), 14.5-17.8 (1H, brs)

[1104] The compound of Example 601 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.50-2.20, 2.20-2.73 and 2.90-4.00 [all 16H, m, 1.62 (s), 2.59 (s), 3.24 (s)], 7.16-7.69 (12H, m), 9.42 (1H, s)

[1105] The compound of Example 606 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.00, 2.55-2.90, 3.35-3.70 and 4.40-4.60 [all 27H, m, 1.57 (s)], 7.00-7.34 (3H, m)

[1106] The compound of Example 607 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.09, 2.56-2.97, 3.30-3.65, 4.40-4.60 and 4.71-4.82 (all 24H, m), 6.95-7.28 (3H, m)

[1107] The compound of Example 608 ¹H-NMR (250 MHz, DMSO-d₆) δ ppm: 1.15-1.55, 1.70-2.35, 2.55-3.16, 3.44-3.65, 4.20-4.40 and 4.70-5.07 (all 9H, m), 6.49-6.57, 6.57-6.85, 6.9-7.05 and 7.05-7.5 (all 8H, m), 7.62-7.75 (2H, m)

[1108] The compound of Example 609 ¹H-NMR (250 MHz, DMSO-d₆) δ ppm: 1.15-2.14, 2.14-4.40 and 4.90-5.54 (all 12H, m), 6.65 and 6.72 (all 1H, each d, J=8.3 Hz), 6.92-7.46 and 7.60-7.81 (all 8H, m)

[1109] The compound of Example 610 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.15-2.63, 2.27-3.18, 3.55-4.06 and 5.82-6.03 (all 8H, m), 7.46 (1H, d, J=8.3 Hz), 7.78 (1H, dd, J=2.4 Hz, J=8.3 Hz), 8.16 (1H, d, J=2.4 Hz), 8.21-8.33 (2H, m), 8.54-8.70 (2H, m), 10.87 (1H, s)

[1110] The compound of Example 611 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.49-1.76, 1.86-2.22, 2.67-3.09 and 4.90-5.08 (all 8H, m), 6.51 (1H, d, J=8.3 Hz), 6.89 (1H, dd, J=2 Hz, J=8.3 Hz), 7.13-7.35 (3H, m), 7.42-7.56 (2H, m)

[1111] The compound of Example 613 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.27-1.70, 1.80-2.30, 2.68-3.37, 3.40-3.85, 4.35-4.58 and 5.08-5.20 (all 9H, m), 6.47 and 6.54 (all 1H, each d, J=8.3 Hz), 6.86-7.01 (1H, m), 7.15 and 7.32 (all 1H, each d, J=2 Hz), 7.35-7.56 (4H, m)

[1112] The compound of Example 614 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-3.90, 4.40-4.55 and 5.03-5.20 (all 28H, m), 6.45-6.65 (1H, m), 6.70-7.35 (6H, m), 7.65-7.95 (1H, m)

[1113] The compound of Example 615 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.80-3.90, 4.35-4.56, 5.08-5.20 and 6.45-6.67 (1H, m), 6.90-7.55 (6H, m), 7.80-8.25 and 8.75-8.85 (all 1H, m)

[1114] The compound of Example 616 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.00-3.95, 4.37-4.57 and 5.00-5.17 (all 22H, m), 6.45 and 6.50 (all 1H, each d, J=8.3 Hz), 6.90 (1H, dd, J=2.3 Hz, J=8.3 Hz), 6.96-7.06 and 7.29-7.36 (all 2H, m), 7.44-7.68 (4H, m)

[1115] The compound of Example 617 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.85-3.92, 4.35-4.52 and 4.95-5.15 (all 26H, m), 6.40-6.55 (1H, m), 6.85-6.95 (1H, m), 6.95-7.15 (1H, m), 7.30-7.70 (4H, m)

[1116] The compound of Example 618 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.20, 2.52-3.90, 4.40-4.59 and 5.08-5.26 (all 22H, m), 6.54-6.68 (1H, m), 6.87-7.44 (6H, m)

[1117] The compound of Example 619 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.21, 2.47-3.01, 3.07-3.32, 3.41-3.78, 4.35-4.57 and 5.08-5.23 (all 19H, m), 6.00-6.51 (1H, brs), 6.59 (1H, d, J=8.3 Hz), 6.89-7.41 (6H, m)

[1118] The compound of Example 622 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.76-2.21, 2.22-4.31, 4.38-4.64 and 5.01-5.24 [all 23H, m, 2.41 (s), 2.46 (s)], 6.38-7.43 (6H, m)

[1119] The compound of Example 623 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.73-5.18 (24H, m), 6.52-8.03 (8H, m), 12.50-13.30 (1H, m)

[1120] The compound of Example 624 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.93 (3H, t, J=7.2 Hz), 1.10-2.30 (8H, m), 2.56-4.30 (5H, m), 3.65 and 3.70 (all 3H, s), 3.88 (2H, t, J=6.5 Hz), 4.38-5.33 (1H, m), 6.51-7.40 (8H, m)

[1121] The compound of Example 626 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.22 (4H, m), 2.40-5.23 (5H, m), 2.52 and 2.56 (all 3H, s), 3.72 and 3.73 (all 3H, s), 6.45-7.70 (10H, m)

[1122] The compound of Example 627 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.17-2.21 (4H, m), 2.61-3.02 (2H, m), 3.09-3.85 (1H, m), 3.69 (3H, s), 4.01-4.27 (1H, m), 4.43-5.18 (1H, m), 4.94 and 5.10 (all 2H, s), 6.46-6.67 (1H, m), 6.83-7.50 (11H, m)

[1123] The compound of Example 629 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.09-2.32 (4H, m), 2.56-5.33 (5H, m), 3.69 and 3.74 (all 3H, s), 6.53-7.78 (12H, m)

[1124] The compound of Example 630 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-2.18 (4H, m), 1.18 and 1.34 (all 9H, s), 2.33-5.24 (5H, m), 2.45 and 2.49 (all 3H, s), 7.32 (3H, s), 6.43-7.51 (7H, m)

[1125] The compound of Example 631 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.08-2.25 (4H, m), 1.18 and 1.33 (all 9H, s), 2.34-3.96 (5H, m), 2.45 and 2.50 (all 3H, s), 6.47-7.50 (7H, m), 9.00 (1H, brs)

[1126] The compound of Example 632 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.35 (7H, m), 2.58-3.28 (3H, m), 3.35-5.20 (10H, m), 6.15-7.56 (6H, m)

[1127] The compound of Example 633 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.16-2.22 (7H, m), 2.58-3.29 (3H, m), 3.35-4.18 (6H, m), 4.45-5.21 (1H, m), 6.12-7.48 (6H, m), 10.82 (1H, brs)

[1128] The compound of Example 634 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.13-2.21 (4H, m), 2.36-4.31 (4H, m), 2.49 (3H, s), 4.33-5.13 (1H, m), 6.76-7.88 (11H, m), 12.43 (1H, brs)

[1129] The compound of Example 637 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.33, 2.33-3.99, 3.99-4.31, 4.50-4.65 and 5.05-5.18 (all 15H, m), 6.50-7.70 and 8.10-8.20 (all 12H, m)

[1130] The compound of Example 640 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-2.26, 2.35-3.90, 4.43-4.66 and 5.03-5.22 (all 15H, m), 6.40-6.70 (1H, m), 6.73-6.95 (1H, m), 6.95-7.65 (6H, m), 8.50-8.75 (2H, m)

[1131] The compound of Example 641 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.22-2.35, 2.5-3.3, 3.4-3.9, 4.35-4.7 and 5.0-5.3 (all 18H, m), 6.65 (1H, d, J=8.3 Hz), 6.85-7.5 (9H, m), 7.6-7.8 (1H, m)

[1132] The compound of Example 642 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-1.65, 1.9-2.25, 2.6-3.1, 3.1-3.35, 3.4-3.75, 4.3-4.6 and 4.9-5.6 (all 14H, m), 6.62 (1H, d, J=8.3 Hz), 6.85-7.5 (9H, m), 7.6-7.8 (1H, m)

[1133] The compound of Example 643 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.78-1.06, 1.14-2.19, 2.59-3.30, 3.40-4.65 and 4.94-5.16 [all 21H, m, 3.69 (s)], 6.78-7.75 and 8.56-8.70 [all 8H, 7.45 (s)]

[1134] The compound of Example 644 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.92 (6H, d, J=6.71 Hz), 1.19-2.32, 2.55-4.62 and 4.95-5.16 (all 12H, m), 6.32-7.95 [all 9H, m, 7.55 (s)]

[1135] The compound of Example 645 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.31, 2.52-4.70 and 4.90-5.15 [all 14H, m, 3.69 (s)], 6.79-7.81 and 8.55-8.72 (all 8H, m)

[1136] The compound of Example 646 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-2.35, 2.62-4.71 and 4.98-5.19 [all 16H, , 3.70 (s)], 6.81-7.92 (all 7H, m, 7.52 (d, J=2.06 Hz)]

[1137] The compound of Example 649 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.98-4.60 and 4.78-4.90 (all 13H, m), 6.05-6.21 and 6.40-8.08 (all 7H, m)

[1138] The compound of Example 647 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.25-2.32, 2.60-3.31, 3.40-4.68 and 5.05-5.20 [all 18H, m, 3.69 (s)], 6.58-7.81 (8H, m)

[1139] The compound of Example 648 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-2.32, 2.58-3.90, 4.00-4.68 and 5.00-5.18 [all 18H, m, 3.70 (s)], 6.80-7.64 (7H, m)

[1140] The compound of Example 650 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.89 (2H, t, J=6 Hz), 4.35 (2H, t, J=6 Hz), 7.0 (1H, d, J=7 Hz), 7.2-7.7 (10H, m), 7.99 (1H, d, J=2.5 Hz)

[1141] The compound of Example 651 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.33 (3H, t, J=7 Hz), 3.44 (2H, dt, J=6.4 Hz, J=2.4 Hz), 3.98 (2H, t, J=6.4 Hz), 4.23 (2H, q, J=7 Hz), 6.41 (1H, t, J=2.4 Hz), 6.86 (1H, d, J=8.6 Hz), 7.0 (1H, dd, J=8.4 Hz, J=2.4 Hz), 7.35-7.70 (10H, m)

[1142] The compound of Example 652

[1143]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.29 (3H, t, J=7 Hz), 1.8-2.3 (2H, m), 2.6-2.8 (1H, m), 2.8-3.0 (1H, m), 3.3-3.56 (1H, m), 3.85-4.1 (2H, m), 4.22 (2H, q, J=7 Hz), 6.69 (1H, d, J=8.6 Hz), 6.89 (1H, dd, J=8.6 Hz, J=2.4 Hz), 7.2-7.7 (10H, m)

[1144] The compound of Example 653 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-1.7 (5H, m), 1.7-2.1 (5H, m), 2.4-2.75 (1H, m), 2.85 (2H, t, J=6 Hz), 4.3 (2H, t, J=6 Hz), 7.0 (1H, d, J=8.8 Hz), 7.19-7.27 (3H, m), 7.40-7.45 (2H, m), 7.96 (1H, d, J=2.5 Hz)

[1145] The compound of Example 654 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.9 (2H, t, J=6.4 Hz), 3.96 (3H, s), 4.31 (2H, t, J=6.4 Hz), 6.94-7.1 (2H, m), 7.35-7.40 (2H, m), 7.77 (1H, d, J=8.0 (1 H, d, J=2.5 Hz)

[1146] The compound of Example 655 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.85-2.05 (1H, m), 2.15-2.35 (1H, m), 2.65 (1H, m), 2.85 (1H, m), 3.35-3.55 (1H, m), 3.85-4.10 (2H, m), 6.70 (1H, d, J=8.6 Hz), 6.90 (1H, dd, J=8.6 Hz, J=2.4 Hz), 7.25-7.65 (10H, m)

[1147] The compound of Example 656 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-1.55 (5H, m), 1.33 (3H, t, J=7.2 Hz), 1.65-2.0 (5H, m), 2.45-2.65 (1H, m), 3.35-3.5 (2H, m), 3.94 (2H, t, J=6.4 Hz), 4.22 (2H, q, J=7.2 Hz), 6.40 (1H, t, J=2.3 Hz), 6.85 (1H, d, J=8.7 Hz), 7.05 (1H, dd, J=8.7 Hz, J=2.3 Hz), 7.15 (2H, d, J=8.2 Hz), 7.34 (2H, d, J=8.2 Hz), 7.65 (1H, d, J=2.3 Hz)

[1148] The compound of Example 657 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-1.60 (5H, m), 1.70-2.0 (6H, m, 2.10-2.35 (1H, m), 2.35-2.65 (1H, m), 2.67 (1H, dd, J=16 Hz, J=6 Hz), 2.90 (1H, dd, J=16 Hz, J=6 Hz), 3.35-3.55 (1H, m), 3.85-4.05 (2H, m), 6.70 (1H, d, J=8.7 Hz), 6.89 (1H, dd, J=8.7 Hz, J=2.3 Hz), 7.12 (2H, d, J=8.2 Hz), 7.19 (1H, d, J=2.3 Hz), 7.28 (2H, d, J=8.2 Hz)

[1149] The compound of Example 658 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.85-2.10 (1H, m), 2.15-2.35 (1H, m), 2.68 (1H, dd, J=16 Hz, J=8 Hz), 2.87 (1H, dd, J=16 Hz, J=6.2 Hz), 3.3-3.5 (1H, m), 3.75 (3H, S), 3.8-4.15 (2H, m), 6.4-6.55 (1H, m), 6.88 (1H dd, J=8.6 Hz), J=2.3 Hz), 7.20 (1H, d, J=2.3 Hz), 7.54 (2H, d, J=8.9 Hz), 8.16 (2H, d, J=8.9 Hz)

[1150] The compound of Example 659 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.85-2.10 (1H, m), 2.20-2.40 (1H, m), 2.71 (1H, dd, J=16 Hz, J=8.4 Hz), 2.94 (1H, dd, J=16 Hz, J=6 Hz), 3.35-3.55 (1H, m), 3.85-4.10 (2H, m), 6.70 (1H, d, J=8.6 Hz), 6.90 (1H, dd, J=8.6 Hz, J=2.3 Hz), 7.21 (1H, d, J=2.3 Hz), 7.35-7.70 (9H, m)

[1151] The compound of Example 660 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.80-2.0 (1H, m), 2.10-2.30 (1H, m), 2.62 (1H, dd, J=15.6 Hz, J=8.6 Hz). 2.84 (1H, dd, J=15.6 Hz, J=6 Hz), 3.3-3.5 (1H, m), 3.73 (3H, s), 3.80-4.10 (4H, m), 6.50 (2H, d, J=8.5 Hz), 6.67(1H, d, J=8.5 Hz), 6.89 (1H, dd, J=8.7 Hz, J=2.2 Hz), 7.15-7.35 (3H, m)

[1152] The compound of Example 661 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.75-1.95 (1H, m), 2.10-2.30 (1H, m), 3.63 (1H, dd, J=15.6 Hz, J=8.4 Hz), 2.85 (1H, dd, J=15.6 Hz, J=6.2 Hz), 3.3-3.5 (1H, m), 3.74 (3H, s), 3.80-4.05 (2H, m), 4.61 (2H, s), 6.6 (1H, d, J=8.6 Hz), 6.88 (1H, dd, J=8.6 Hz, J=2.2 Hz), 6.95-7.65, 8.36 [all 11H, m, 8.36(s)]

[1153] The compound of Example 662 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.80-2.10 (1H, m), 2.15-2.30(1H, m), 2.71 (1H, dd, J=16 Hz, J=8 Hz), 2.90 (1H, dd, J=16 Hz, J=6 Hz), 3.3-3.5 (1H, m), 3.75-4.10 (2H, m), 4.60 (2H, s), 6.59 (1H, d, J=8.6 Hz), 6.88 (1H, dd, J=8.6 Hz, J=2.2 Hz), 6.97 (2H, d, J=7.8 Hz), 6.99-7.10 (1H, m), 7.20 (1H, d, J=2.2 Hz), 7.31-7.39 (4H, m), 7.54 (2H, d, J=8.6 Hz), 8.38 (1H, s)

[1154] The compound of Example 663 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.75-1.95 (1H, m), 2.10-2.20 (1H, m), 2.2 (3H, s), 2.60 (1H, dd, J=15.7 Hz, J=8.6 Hz), 2.83 (1H, dd, J=15.7 Hz, J=6 Hz), 3.3-3.4 (1H, m), 3.78 (3H, s), 3.8-4.0 (2H, m), 4.69 (2H, s), 6.60 (1H, d, J=8.7 Hz), 6.87 (2H, dt, J=8.6 Hz, J=2.2 Hz), 6.94-7.01 (1H, m), 7.10-7.50 (5H, m), 7.64 (2H, d, J=8.7 Hz), 7.74 (1H, s), 9.60 (1 H, s)

[1155] The compound of Example 664 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.75-2.00 (1H, m), 2.15-2.35 (1H, m), 2.64 (1H, dd, J=15.7 Hz, J=8.6 Hz), 2.86 (1H, dd, J=15.7 Hz, J=6 Hz), 3.3-3.35 (1H, m), 3.75 (3H, s), 3.80-4.00 (2H, m), 4.72 (2H, s), 6.61 (1H, d, J=8.6 Hz), 6.87 (1H, dd, J=8.8 Hz, J=2.2 Hz), 6.93-7.07 (2H, m), 7.17 (1H, d, J=2.2 Hz), 7.25-7.50 (4H, m), 7.58 (2H, d, J=8.6 Hz), 8.78 (1H, s)

[1156] The compound of Example 665 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.80-2.05 (1H, m), 2.10-2.30 (1H, m), 2.71 (1H, dd, J=16 Hz, J=8.2 Hz), 2.92 (1H, dd, J=16 Hz, J=6 Hz), 3.30-3.5 (1H, m), 3.75-4.10 (2H, m), 4.65 (2H, s), 6.55-7.65 [all 11H, m, 6.60 (d, J=8.6 Hz), 7.57 (d, J=8.6 Hz)], 8.79 (1H, s)

[1157] The compound of Example 666 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.80-2.0 (1H, m), 2.1-2.3 (1H, m), 2.36 (3H, s), 2.63 (1H, dd, J=15.6 Hz, J=8.5 Hz), 2.86 (1H, dd, J=15.6 Hz, J=6 Hz), 3.3-3.5 (1H, m), 3.74 (3H, s), 3.83-3.99 (2H, m), 4.59 (2H, s), 6.60 (1H, d, J=8.6 Hz), 6.78 (2H, d, J=8 Hz), 6.88 (2H, dd, J=8.6 Hz, J=2 Hz), 7.16-7.26 (2H, m) 7.38 (2H, d, J=8.7 Hz), 7.55 (2H, d, J=8.7 Hz), 8.36 (1H, m),

[1158] The compound of Example 667 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.8-2.25, 2.65-4.10 (all 10H, m), 4.68 (2H, s), 6.4-7.85 (all 13H, m), 9.48 (1H, s)

[1159] The compound of Example 668 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.8-3.0 (all 7H, m), 3.25-3.50 (1H, m), 3.70-4.05 (2H, m), 4.56 (2H, s), 6.60 (1H, d, J=8.5 Hz), 6.75-6.90 (4H, m), 7.18-7.26 (2H, m), 7.35 (2H, d, J=8.6 Hz), 7.52 (2H, d, J=8.7 Hz), 8.4 (1H, s)

[1160] The compound of Example 669 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.9-2.25, 2.6-4.1, 4.3-4.75 [all 15H, m, 0.99 (t, J=7.2 Hz)], 6.8-7.5, 7.55-7.65, 8.2-8.5 [all 13H, m, 7.60 (d, J=4 Hz), 8.25 (d, J=4 Hz)]

[1161] The compound of Example 670 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.3-2.2, 2.35-2.5, 2.7-3.9 and 4.4-4.65 [all 15H, m, 2.40 (s), 3.73 (s)], 6.55 (0.6H, d, J=8.3 Hz), 6.89 (1.3H, d, J=8.3 Hz), 7.0-7.5 (all 4H, m), 8.35-8.50 (0.8H, m), 8.9-9.05 (0.25H, m)

[1162] The compound of Example 671 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-2.2, 2.7-3.4, 3.5-3.8 and 4.45-4.65 [all 12H, m, 3.69 (s)], 6.85-7.5 and 8.9-9.1 (all 8H, m)

[1163] The compound of Example 672 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.4-2.3, 2.75-3.25 and 4.75-5.05 (all 8H, m), 6.75-7.45 (all 7H, m), 9.55 and 10.03 (all 1H, each s)

[1164] The compound of Example 673 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.2, 2.6-3.85 and 4.4-4.65 [all 15H, m, 2.83 (s)], 6.21 (0.7H, dd, J=8.7 Hz, J=2.5 Hz), 6.51 (0.6H, d, J=2.5 Hz), 6.6-7.4 (all 5.7H, m)

[1165] The compound of Example 674 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.0-2.1, 2.7-3.9, 4.4-5.3 [all 17H, m, 1.1 (d, J=6 Hz)], 6.0-6.1 and 6.4-7.6 (all 8H, m)

[1166] The compound of Example 675 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-2.2, 2.7-4.0 and 4.45-4.7 (all 13H, m), 5.9 and 6.9-7.7 [all 8H, m, 5.9 (s)]

[1167] The compound of Example 676 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-2.35, 2.75-3.10, 3.10-3.95 and 4.4-4.6 [all 16H, m, 2.79 (s)], 6.3-7.6 (all 7H, m)

[1168] The compound of Example 677 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.1-1.25, 1.25-2.2, 2.7-3.95 and 4.45-4.65 (all 22H, m), 6.85-7.8 (all 7H, m), 7.8-8.5 (1H, m)

[1169] The compound of Example 678 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.05, 2.65-4.0 and 4.3-4.65 [all 15H, m, 4.39 (s)], 5.8-6.85 (1H, m), 6.85-8.15 (all 12H, m)

[1170] The compound of Example 679 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.04-2.20 [all 7H, m, 1.41 (t, J=7.0 Hz)], 2.32-3.32, 3.33-4.30, 4.43-4.70 and 5.00-5.22 (all 13H, m, 2.51 (s), 3.72 (s)], 6.43-7.67 (11H, m)

[1171] The compound of Example 680 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03 (3H, t, J=7.0 Hz), 0.90-2.30 (6H, m), 2.38-3.30, 3.38-4.36, 4.43-4.70 and 5.04-5.23 [all 13H, m, 2.52 (s), 3.72 (s), 3.93 (t)], 6.43-7.64 (11H, m)

[1172] The compound of Example 683 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.24-3.02 (5H, m), 3.04-3.89, 3.90-4.88 and 4.93-5.14 (all 10H, m, 3.71 (s), 3.74 (s), 3.76 (s), 3.82 (s)], 6.49-6.65, 6.71-6.86, 6.94-7.10, 7.11-7.42 and 7.58-7.78 (all 6H, m)

[1173] The compound of Example 684 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-2.23, 2.24-3.93, 4.01-4.31, 4.43-4.70 and 5.01-5.22 [all 18H, m, 2.37 (s), 2.44 (s), 2.53 (s), 2.57 (s), 3.72 (s)], 6.47-7.59 (11H, m)

[1174] The compound of Example 685 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-2.26 (4H, m), 2.56-4.32, 4.45-4.73 and 5.00-5.20 [all 8H, m, 3.71 (s)], 6.68-7.81 (12H, m)

[1175] The compound of Example 686 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-2.37, 2.42-4.39, 4.47-4.75 and 5.04-5.26 [all 15H, m, 2.56 (s), 3.73 (s)], 6.49-7.95 and 8.13-8.49 (all 11H, m)

[1176] The compound of Example 687 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.27 (4H, m), 2.28-4.39, 4.45.4.72 and 5.03-5.27 [all 14H, m, 2.35 (s), 2.41 (s), 2.52 (s), 2.56 (s)], 6.49-7.64 (11H, m)

[1177] The compound of Example 689 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.00-3.76, 4.28-4.55 and 4.81-5.05 [all 15H, m, 2.31 (s), 2.44 (s)], 6.49-7.79 (11H, m), 12.31 (1H, s)

[1178] The compound of Example 690 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.04-2.22 (4H, m), 2.32-3.76, 4.27-4.58 and 4.81-5.08 (all 8H, m), 6.49-8.48 (11H, m), 11.97-12.54 (1H, m)

[1179] The compound of Example 691 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.02-3.86, 4.36-4.62 and 5.01-5.30 [all 26H, m, 2.41 (s), 3.74 (s)], 6.36-7.40 (6H, m)

[1180] The compound of Example 692 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.20-3.01, 3.32-4.28 and 4.78-5.49 [all 23H, m, 2.35 (s), 2.44 (s), 3.82 (s)], 6.55-7.75 (11H, m)

[1181] The compound of Example 693 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-2.05 (10H, m), 2.19-2.95, 3.42-4.25 and 4.75-5.39 [all 21H, m, 2.35 (s)], 6.59-7.55 (7H, m)

[1182] The compound of Example 696 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.48 (3H, d, J=6.6 Hz),1.57-2.13 (2H, m), 2.86-3.13 (2H, m), 3.36-3.65 (1H, m), 4.43-4.63 (1H, m), 4.70-4.93 (1H, m), 6.48-8.00 (12H, m), 10.19 and 10.46 (all 1H, s), 12.68 (1H, brs)

[1183] The compound of Example 700 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.31 (3H, t, J=7.1 Hz), 1.58 (3H, d, J=6.7 Hz), 1.51-2.33 (2H, m), 2.97-3.23 (2H, m), 3.40-3.70 (1H, m), 3.81-4.18 (2H, m), 4.25 (2H, q, J=7.1 Hz), 4.40-4.91 (1H, m), 4.73 (1H, q, J=6.7 Hz), 6.51-7.65 (12H, m), 8.22 (1H, brs)

[1184] The compound of Example 701 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.34 (3H, t, J=7.11 Hz), 2.28-3.00 (2H, m), 3.71-5.12 (all 6H, m), 6.85-7.65 and 7.75-8.45 (all 7H, m)

[1185] The compound of Example 702 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.32 (3H, t, J=7.12 Hz), 2.32-2.90 (2H, m), 3.61-4.49 (all 6H, m), 4.65-5.05 (2H, m), 6.10-7.68 (all 7H, m)

[1186] The compound of Example 703 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.22-1.43 (3H, m), 1.78-2.38 (2H, m), 2.99-3.24 (2H, m), 3.43-3.66 (1H, m), 3.78-4.39 (4H, m), 4.65-4.89 (1H, m), 6.67 (1H, dt, J=7.6 Hz, J=1.3 Hz), 6.70 (1H, dd, J=8.2 Hz, J=1.3 Hz), 6.89-6.99 (1H, m), 7.05 (1H, dd, J=7.3 Hz, J=1.7 Hz), 7.37 (1H, d, J=8.4 Hz), 7.81 (1H, dd, J=8.4 Hz, J=2.1 Hz), 8.10 (1H, d, J=2.1 Hz)

[1187] The compound of Example 704 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.32 (3H, t, J=7.16 Hz), 1.50-1.81 [all 3H, m, 1.59 (d, J=6.71 Hz)], 2.50-2.95 and 3.69-5.15 (all 9H, m), 6.81-8.55 [13H, m, 7.55 (s), 8.26 (s)]

[1188] The compound of Example 705 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.41-1.75 [all 3H, m, 1.59 (d, J=6.76 Hz)], 1.75-2.89, 3.60-4.48 and 4.60-5.10 (all 7H, m), 6.79-8.20 and 8.36-8.88 (all 12H, m)

[1189] The compound of Example 706 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.72-1.10 (6H, m), 1.33 (3H, t, J=7.13 Hz), 1.80-2.10, 2.55-2.90, 3.69-4.59 and 4.75-5.05 [all 11H, m, 7.29 (q, J=7.13 Hz)], 6.71-7.85, 8.59-8.70 [all 8H, m, 6.63 (s)]

[1190] The compound of Example 707 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.33 (3H, t, J=6.17 Hz), 2.31-2.95 and 3.39-5.10 (all 12H, m), 6.72-7.89 (8H, m)

[1191] The compound of Example 708 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.34 (3H, t, J=7.15 Hz), 2.55-3.05, 3.70-4.61 and 4.79-5.08 [all 12H, m, 4.29 (q, J=7.15 Hz), 4.46 (t, J=7.88 Hz)], 6.81-7.72 (7H, m)

[1192] The compound of Example 709 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.89 (6H, d, J=6.69 Hz), 1.70-2.05, 2.30-4.20 and 4.45-4.82 (all 9H, m), 6.85-7.79, 8.10-8.20 and 9.65-9.95 [all 8H, m, 8.14 (s), 9.70 (s)]

[1193] The compound of Example 710 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.05-5.05 (11H, m), 6.70-8.00 (7H, m)

[1194] The compound of Example 711 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.99-1.98, 2.18-3.00 and 3.64-4.01 [all 18H, m, 2.34 (s)], 6.50-7.61 and 8.40-8.73 (all 8H, m)

[1195] The compound of Example 712 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.43 (3H, s), 2.62-3;00, 3.71-4.20 and 4.55-5.29 [all 7H, m, 3.82 (s)], 6.62-7.65 and 8.45-8.75 [all 12H, m, 7.42 (d, J=8.45 Hz)]

[1196] The compound of Example 713 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-3.81 and 4.81-5.35 [all 21H, m, 2.37 (s)], 6.35-7.50 (7H, m)

[1197] The compound of Example 714 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.55-4.05 and 4.85-5.25 [all 13H, m, 2.46 (s), 3.81 (s)], 6.40-7.61 (11H, m)

[1198] The compound of Example 715 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.04-2.01, 2.18-3.10, 3.56-4.49 and 4.61-5.65 [all 20H, m, 2.35 (s)], 6.51-7.65 (7H, m)

[1199] The compound of Example 716 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.34 (3H, t, J=7.08 Hz), 2.15-3.10, 3.61-4.51 and 4.78-5.11 [all 14H, m, 2.44 (s), 3.83 (s)], 6.61-7.58 (11H, m)

[1200] The compound of Example 717 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.01-2.97, 3.51-4.28 and 4.75-5.19 [all 20H, m, 2.34 (s)], 6.40-7.70 (8H, m)

[1201] The compound of Example 718 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.29-2.94, 3.56-4.29 and 4.75-5.08 [all 12H, m, 2.43 (s), 3.82 (s)], 6.59-7.65 (7H, m), 8.55-9.07 (1H, m)

[1202] The compound of Example 719 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.53 (9H, s), 2.51-2.96, 3.72-4.31 and 4.51-5.18 (all 6H, m), 6.85-7.62 and 7.78-8.41 (all 7H, m)

Example 721

[1203] To dimethylsulfide (170 ml) is added dropwise with stirring aluminum chloride (23.6 g) under ice-cooling, and further thereto is added dropwise a solution of 5-methoxycarbonylmethyl-1-[4-(2-phenoxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (16.76 g) in dichloromethane (150 ml), and the mixture is stirred at room temperature for two hours. The reaction mixture is poured into a mixture of conc. hydrochloric acid and crashed ice, and the mixture is extracted with dichloromethane. The organic layer is washed with water, dried over magnesium sulfate, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=30:1) to give 5-carboxymethyl-1-[4-(2-phenoxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (13.67 g) as white powder.

[1204] M.p. 102-106° C.

Example 722

[1205] 7-Chloro-1-[2-methyl-4-(2-acetylacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.48 g) is dissolved in tetrahydrofuran (7 ml), and thereto is added a 5N aqueous sodium hydroxide solution (0.5 ml), and the mixture is stirred at room temperature for two hours. The reaction solution is neutralized with a 2N hydrochloric acid, and extracted with ethyl acetate. The extract is dried over magnesium sulfate, filtered, and concentrated. To the resulting residue is added n-hexane/ethyl acetate (1:1), and the mixture is washed, filtered, and the obtained powder is dried to give 7-chloro-1-[2-methyl-4-(2-hydroxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.38 g) as white powder.

[1206] M.p. 194-195° C.

Example 723

[1207] 1-[2-Methyl-4-(2-chloroacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.8 g) is dissolved in dimethylformamide (5 ml), and thereto are added potassium carbonate (0.47 g), sodium iodide (0.51 g) and 5,6,7,8-tetrahydro-1-naphthol (0.40 g), and the mixture is stirred at 60° for three hours. To the reaction solution is added ethyl acetate, and the mixture is washed with a saturated aqueous potassium hydrogen sulfate solution and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated. The resulting residue is allowed to stand for one day, washed with dichloromethane, filtered, and dried to give 1-{2-methyl-4-[2-(5-tetrahydronaphthyloxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.72 g) as white powder.

[1208] M.p. 230-232° C. (decomposed)

[1209] The suitable starting compounds are treated in the same manner as in Example 723 to give the compounds of Examples 55-58, 147, 148, 150-156, 158-162, 165-166, 160, 170, 176-179, 186-196, 198, 200-207, 212, 213, 215, 217, 222-224, 228-232, 338-346, 355-358, 363, 399-402, 445-448, 583, 593, 598, 661-669, 696-700 and 704-705.

Example 724

[1210] A mixture of 1-(4-amino-2-chlorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (1 g), triphosgen (0.3 g) and o-dichlorobenzene (10 ml) is heated with stirring at 130-140° C. for four hours. To the mixture is added triethylamine (0.8 ml), and the mixture is stirred for 0.5 hour, and thereto is further added triethylamine (0.8 ml), and the mixture is stirred for 0.5 hour. To the mixture is added 1,2,3,4-tetrahydroisoquinoline (0.38 ml), and the mixture is heated with stirring at 80° C. for one hour. The mixture is diluted with dichloromethane, and washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and evaporated to remove the solvent to give an oily residue (2.9 g). The residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=1:1) to give 1-[4-(2-tetrahydroisoquinolylcarbonylamino)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.47 g) as colorless amorphous.

[1211]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.15, 2.70-3.10 and 4.80-5.00 (all 10H, m), 3.66 and 3.76 (all 2H, each t, J=5.8 Hz), 4.60 and 4.71 (all 2H, each s), 6.70-7.50 (12H, m)

Example 725

[1212] To a solution of 1-(4-amino-2-chlorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.8 g) in o-dichlorobenzene (5 ml) is added triphosgen (0.26 g), and the mixture is stirred at 120° C. for three hours. To the mixture is added triethylamine (0.27 g), and the mixture is stirred at 120° C. for two hours. To the mixture is added (4-pyridyl)methanol (0.29 g), and the mixture is stirred at 120° C. for two hours. To the reaction solution is added ethyl acetate, and the mixture is washed with water, and the organic layer is dried over magnesium sulfate, filtered, and evaporated to remove the solvent. The resulting residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=1:5→dichloromethane:methanol=25:1), and the residue is washed with methanol/diethyl ether to give 1-{4-[(4-pyridyl)methoxycarbonylamino]-2-chlorobenzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.45 g) as white powder.

[1213] M.p. 181-184° C.

Example 726

[1214] To chloroform (5 ml) is added triphosgen (0.72 g), and thereto is added with stirring 2-phenoxyethanol (1.0 g) under ice-cooling, during which the temperature of the reaction solution is kept at below 10° C., and the mixture is stirred at 0° C. for one hour. To the reaction solution are added with stirring dropwise 1-(4-amino-2-chlorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (1.9 g) and a solution of piperidine (2.5 g) in chloroform (30 ml) under ice-cooling. The mixture is stirred at room temperature for three hours, washed with a saturated aqueous potassium hydrogen sulfate solution, distilled water and a saturated aqueous sodium hydrogen carbonate solution, and dried over magnesium sulfate, filtered, and evaporated to remove the solvent. The residue is recrystallized from diethyl ether to give 1-[4-(2-phenoxyethoxy-carbonylamino)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (1.3 g) as white powder.

[1215] M.p. 144-146° C.

[1216] The suitable starting compounds are treated in the same manner as in Examples 725 and 726 to give the compounds of Examples 157, 167, 197,199, 214, 233, 234, 406, 407, 420, 538, 540, 549, 550, 552, 556, 557, 559, 568, 587, 588, 596, 604, 643, 645, 647, 695, 706, 707 and 709.

Example 727

[1217] A mixture of 5-ethoxycarbonylmethyl-1-[4-(2-chloroethoxycarbonylamino)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (0.9 g), potassium carbonate (0.40 g) and sodium iodide (0.43 g) in dimethylformamide (15 ml) is stirred at 8° C. for 8 hours. To the reaction solution is added ethyl acetate, and the mixture is washed with water, and the organic layer is dried over magnesium sulfate, filtered, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=30:1) to give 5-ethoxycarbonylmethyl-1-[4-(2-oxotetra-hydrooxazol-3-yl)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (0.65 g) as colorless amorphous.

[1218]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.34 (3H, t, J=7.15 Hz), 2.55-3.05, 3.70-4.61 and 4.79-5.08 [all 12H, m, 4.29 (q, J=7.15Hz, 4.46 (t, J=7.88 Hz)], 6.81-7.72 (7H, m)

[1219] The suitable starting compounds are treated in the same manner as in Example 727 to give the compounds of Examples 511, 594, 646, 649, 694 and 710.

Example 728

[1220] To a mixture of 1-[4-(1-piperazinyl)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.25 g), 37% formaldehyde (0.45 g) and sodium tetrahydro-1H-benzazepine (0.25 g), 37% formaldehyde (0.45 g) and sodium (0.12 g) under ice-cooling, and the mixture is stirred at room temperature for one hour. To the reaction solution is added ethyl acetate, and the mixture is washed with a 2N aqueous sodium hydroxide solution and distilled water. The organic layer is dried over magnesium sulfate, filtered, and concentrated, and the resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=10:1) to give 1-[4-(4-methyl-1-piperazinyl)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.10 g) as white powder.

[1221] M.p. 138-140° C.

[1222] The suitable starting compounds are treated in the same manner in Example 728 to give the compounds of Examples 416, 417, 457, 515, 523, 524, 677 and 678.

Example 729

[1223] 1-[4-Nitro-2-chlorobenzoyl]-1,5-benzodiazepine (5 g) and ethyl bromoacetate (16.7 ml) are dissolved in acetonitrile (100 ml), and thereto is added dropwise 1,8-diazabicyclo[5.4.0]-7-undecene (11.3 ml). The mixture is refluxed for two days, concentrated, and thereto are added water and chloroform, and extracted. The extract is dried over sodium carbonate, and purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=4:1→1:1) to give 1-(4-nitro-2-chlorobenzoyl)-5-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (4.4 g) as pale yellow oil.

[1224]¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.22-1.43 (3H, m), 1.78-2.38 (2H, m), 2.99-3.24 (2H, m), 3.43-3.66 (1H, m), 3.78-4.39 (4H, m), 4.65-4.89 (1H, m), 6.67 (1H, dt, J=7.6 Hz, J=1.3 Hz), 6.70 (1H, dd, J=8.2 Hz, J=1.3 Hz), 6.89-6.99 (1H, m), 7.05 (1H, dd, J=7.3 Hz, J=1.7 Hz), 7.37 (1H, d, J=8.4 Hz), 7.81 (1H, dd, J=8.4 Hz, J=2.1 Hz), 8.10 (1H, d, J=2.1 Hz)

[1225] The suitable starting compounds are treated in the same manner as in Example 729 to give the compounds of Examples 692-702, 704-710 and 715-720.

Example 730

[1226] 5-Cyanomethyl-1-(4-phenyl-2-chlorobenzoyl)-2,3,4,5-tetrahyclro-1H-benzazepine (1 g), ammonium chloride (0.4 g) and sodium azide (0.48 g) are suspended in dimethylformamide (10 ml), and the mixture is heated at 110-120° C. for 16 hours. To the mixture are added ammonium chloride (0.4 g) and sodium azide (0.48 g), and the mixture is heated for 16 hours. The mixture is evaporated to remove dimethylformamide, and the resultant is acidified with a 1N hydrochloric acid. The mixture is extracted with chloroform, and the organic layer is washed with water, dried over magnesium sulfate, and concentrated.

[1227] The residue is purified by silica gel column chromatography (solvent; dichloromethane→dichloromethane:methanol=20:1), and the resulting oily product is crystallized from diethyl ether to give 5-(5-tetrazolyl)methyl-1-(4-phenyl-2-chlorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.9 g) as white powder.

[1228] M.p. 191-194° C.

[1229] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

Example 731 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 732 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Methanol/diethyl ether M.p. 136-138° C. Form: Free Example 733 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 734 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 735 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 736 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 737 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p.: 196-198° C. Form: Free Example 738 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether/n-hexane M.p. 124-126° C. Form: Free Example 739 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Methanol M.p. 160-162° C. Form: Free Example 740 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 741 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 742 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 743 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 744 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether/n-hexane Form: Free Example 745 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 746 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: n-Hexane/ethyl acetate M.p. 162-164° C. Form: Free Example 747 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 748 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 749 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 750 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 118-119° C. Form: Free Example 751 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 752 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 753 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 754 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 755 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 756 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Dihydrochloride Example 757 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Ethanol M.p. 201.5-204° C. Form: Hydrochloride Example 758 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 120-122° C. Form: Free Example 759 Structure:

X: —CH₂— R¹: H R²:H R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 760 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 761 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 762 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 147-148° C. Form: Free Example 763 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether M.p. 178-179° C. Form: Free Example 764 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 765 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless flakes Solvent for recrystallization: Methanol/chloroform/diethyl ether M.p. >300° C. Form: Free Example 766 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether Form: Free Example 767 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether Form: Free Example 768 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether Form: Free Example 769 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 770 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 771 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 772 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Yellow powder M.p. 130-133° C. Form: Free Example 773 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 774 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 775 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 776 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate M.p. 174.5-175.5° C. Form: Free Example 777 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Brown amorphous Form: Free Example 778 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 779 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 780 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Yellow powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 781 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 782 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder M.p. 123-125° C. Form: Free Example 783 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 784 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 785 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 786 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 787 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 788 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 789 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 790 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Yellow amorphous Form: Free Example 791 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Yellow powder M.p. 135-139° C. Form: Free Example 792 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 793 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: White powder M.p. 123-125° C. Form: Free Example 794 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 795 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 796 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Pale yellow amorphous Form: Free Example 797 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Free Example 798 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 799 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Crystalline form: Pale yellow powder Solvent for recrystallization: Chloroform/diethyl ether Form: Free Example 800 Structure:

X: —CH₂— R¹: 7-Cl R²: H R³: H Example 801 Structure:

X: —CH₂— R¹: H R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 802 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 803 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 804 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 805 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 806 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 807 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 808 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 809 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 810 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 811 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CONH(CH₂)₂N(C₂H₅)₂ R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 812 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 813 Structure:

X: —CH₂— R¹: 7-Cl

R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 814 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Chloroform/diethyl ether Form: Hydrochloride Example 815 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂H R³: H Form: Hydrochloride Example 816 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate/n-hexane Form: Free Example 817 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 818 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Yellow viscous oil Form: Free Example 819 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 820 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale yellow oil Form: Free Example 821 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 822 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Pale yellow oil Form: Free Example 823 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂H R³: H Crystalline form: Pale yellow amorphous Form: Free Example 824 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 825 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 826 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Hydrochloride Example 827 Structure:

X: —CH₂— R¹: H R²: —CH₂CN R³: H Crystalline form: White powder Form: Free Example 828 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Form: Free Example 829 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: Pale yellow powder Form: Free Example 830 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder M.p. 170° C. Form: Free Example 831 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder M.p. 177-178° C. Form: Free Example 832 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate/n-hexane M.p. 87-89° C. Form: Free Example 833 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Slightly yellow amorphous Form: Free Example 834 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 835 Structure:

X: —CH₂— R¹: H R²: H R³: H Crystalline form: White powder Form: Free Example 836 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: Yellow oil Form: Free Example 837 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate/n-hexane M.p. 99-101° C. Form: Free Example 838 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 839 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 840 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 841 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 842 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Pale yellow powder Form: Free Example 843 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: White powder Form: Free Example 844 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 845 Structure:

X: —CH₂— R¹: H

R³: H Crystalline form: Colorless amorphous Form: Free Example 846 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Acetone M.p. 185-187° C. Form: Free Example 847 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl/acetate/n-hexane M.p. 148.5-150.5° C. Form: Free Example 848 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Ethyl acetate/n-hexane M.p. 160-162° C. Form: Free Example 849 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 850 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Yellow oil Form: Free Example 851 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Slightly yellow amorphous Form: Free Example 852 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 853 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 854 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 855 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 856 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 857 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 858 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 859 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂H R³: H Crystalline form: Colorless amorphous Form: Free Example 860 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 861 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 862 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂CH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 863 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂CO₂H R³: H Crystalline form: White powder Form: Free Example 864 Structure:

X: —CH₂— R¹: 7-Cl R²: —CH₂COOH R³: H Crystalline form: White powder Form: Free Example 865 Structure:

X: —CH₂— R¹: H R²: —CH₂COOCH₃ R³: H Crystalline form: Colorless amorphous Form: Free Example 866 Structure:

X: —CH₂— R¹: H R²: —CH₂COOH R³: H Crystalline form: Colorless amorphous Form: Free Example 867 Structure:

X: —CH₂— R¹: H R²: —CH₂CO₂CH₃ R³: H Crystalline form: White powder Solvent for recrystallization: Diethyl ether Form: Free

[1230] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

Example 868 Structure:

R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 869 Structure:

R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 870 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 871 Structure:

R¹: H R² and R³: ═O Crystalline form: Colorless amorphous Form: Free Example 872 Structure:

R¹: H R² and R³: ═O Crystalline form: White powder M.p. 168-171° C. Form: Free Example 873 Structure:

R¹: H R²: H R³: H Crystalline form: Brown amorphous Form: Free Example 874 Structure:

R¹: H R²: H R³: H Crystalline form: Brown amorphous Form: Free Example 875 Structure:

R¹: H R²: H R³: H Crystalline form: White powder Form: Free Example 876 Structure:

R¹: H R²: H R³: H Crystalline form: Colorless amorphous Form: Free Example 877 Structure:

R¹: H R² and R³: ═O Crystalline form: Yellow amorphous Form: Free Example 878 Structure:

R¹: H R² and R³: ═O Crystalline form: Yellow amorphous Form: Free Example 879 Structure:

R¹: H R² and R³: ═O Crystalline form: Brown amorphous Form: Free Example 880 Structure:

Y: ═NH R¹: H R² and R³: ═O Crystalline form: White powder Form: Free Example 881 Structure:

R¹: H R² and R³: ═O Crystalline form: Brown oil Form: Free Example 882 Structure:

R¹: H R² and R³: ═O Crystalline form: White powder Form: Free Example 883 Structure:

Y: ═NH R¹: H R² and R³: ═O Crystalline form: Brown amorphous Form: Free Example 884 Structure:

R¹: H R² and R³: ═O Crystalline form: Brown amorphous Form: Free Example 885 Structure:

R¹: H R² and R³: ═O Crystalline form: Brown powder Form: Free

[1231] The data of NMR analysis of the compounds of the above Examples are as follows.

[1232] NMR analysis:

[1233] The compound of Example 741 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.08-1.88 [9H, m, (1.22,1.35, each 3H, each d, J=6.0 Hz)], 1.88-2.61 [11H, m, (2.33, 2.43 each s)], 2.61-4.04, 4.31-4.70, 4.98-5.19 (total 10H, m), 6.12-7.43 (7H, m)

[1234] The compound of Example 742 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-2.59 [15H, m, (2.33, 2.45, each s)], 2.59-3.09 (2H, m), 3.09-4.01, 4.43-4.64 (total 6H, m), 4.93, 5.09 (total 2H, each s), 6.24-7.51 (12H, m)

[1235] The compound of Example 743 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.08-2.61 [15H, m, 2.34 (s)], 2.61-3.02 (2H, m), 3.02-4.11, 4.43-4.64, 4.90-5.12 (total 6H, m), 5.30 (1H, s), 6.00-7.45 (7H, m)

[1236] The compound of Example 754 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.82-1.14 [6H, m, 0.95,1.04, (each d, J=6.7 Hz)], 1.15-1.93 (1H, m), 1.95-2.59 [14H, m, 2.33, 4.45, (each s)], 2.59-4.02, 4.45-4.67, 4.98-5.17 (total 11H, m), 6.12-7.46 (7H, m)

[1237] The compound of Example 755 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.92, 0.99 (total 6H, each t, J=7.3 Hz), 1.19-2.59 [18H, m, 2.33, 2.44, (each s)], 2.59-4.09, 4.41-4.65, 4.95-5.18 [total 11H, m, 3.83, 3.98, (each t, J=6.5 Hz)], 6.11-7.45 (7H, m)

[1238] The compound of Example 760 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.50, 0.95 (total 6H, each d, J=6.5 Hz), 1.01-1.32 [7H, m, 1.04 (3H, d, J=6.7 Hz)], 1.48-3.18 [10H, m, 2.49 (s)], 3.30-4.65, 5.46-5.72 [total 5H, m, (3.75, d, J=6.5 Hz)], 6.40-7.39 (8H, m)

[1239] The compound of Example 761 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.50 (3H, d, J=6.5 Hz), 0.85-1.29 [7H, m, 0.95 (3H, d, J=6.5 Hz), 0.99, 1.16 (total 3H, each t, J=5.5 Hz)], 1.35-2.18 (10H, m), 2.19-2.58 [5H, m, 2.49 (s)], 2.58-2.78, 2.89-3.18 (total 2H, m), 3.30-4.65, 5.41-5.67 (total 6H, m), 6.81-7.40 (8H, m)

[1240] The compound of Example 816 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.21 (4H, m), 2.33-2.55, 3.09-3.87, 4.39-4.62 [total 11 H, m, (2.45, 3.69 each s)], 2.60-3.05 (2H, m), 4.81-5.19 [2H, m, 4.93, 5.09 (each s)], 6.25-7.53 (12H, m)

[1241] The compound of Example 817 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.19 (4H, m), 2.44,2.47 (total 3H, each s), 2.11-3.08 (2H, m), 3.08-3.90, 4.39-4.62, 4.79-5.31 [total 7H, 4.89, 5.06 (total 2H, eash s)], 6.25-7.52 (12H, m)

[1242] The compound of Example 818 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-2.17 [10H, m, 1.24,1.35, (each d, J=6.0 Hz)], 2.32-2.59 [3H, m, 2.43 (s)], 2.61-3.32 (3H, m), 3.41-3.92 [6H, m, 3.70 (s)], 4.29-4.63, 5.01-5.22 (total 2H, m), 6.18-7.42 (7H, m)

[1243] The compound of Example 819 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.09-2.22 [10H, m, 1.22, 1.35 (each d, J=6.0 Hz)], 2.30-2.58 [3H, m, 2.43, 2.47 (each s)], 2.11-4.01 (4H, m), 4.28-4.70, 4.99-5.22 (total 2H, m), 6.13-7.48 (8H, m)

[1244] The compound of Example 838 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.96, 1.04 (total 6H, each d, J=6.7 Hz), 1.18-2.20 (4H, m), 2.44, 2.48 (total 3H, each s), 2.61-3.31, 3.39-4.16, 5.02-5.27 (total 8H, m), 6.19-7.42 (8H, m)

[1245] The compound of Example 839 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.92, 0.99 (total 3H, each t, J=7.2 Hz), 1.15-2.22 (8H, m), 2.43, 2.47 (total 3H, each s), 2.62-3.31, 3.36-4.09, 4.38-4.65, 5.01-5.23 (total 7H, m, (3.82, 3.97, each t, J=6.5 Hz)), 6.17-7.41 (8H, m)

[1246] The compound of Example 765 ¹H-NMR (200 MHz, CDCl₃+DMSO-d₆) δ ppm: 1.2-2.3 (4H, m), 2.5-3.4, 4.7-5.1, 5.3-5.6 (total 4H, each m), 6.5-7.5 (9H, m), 7.60 (1H, dd, J=7.5 Hz, 7.5 Hz), 7.95 (1H, d, J=7.5 Hz), 11.43 (1H, s)

[1247] The compound of Example 731 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.25-4.30, 4.6-4.85 [total 27H, m, 2.49 (s), 2.84 (s), 2.94 (s)], 6.85-8.0 (total 7H, m)

[1248] The compound of Example 733 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.1-2.1, 2.4-4.1, 4.1-4.7 (total 24H, m), 6.7-7.8, 7.8-8.0, 8.35-8.7 (total 7H, m), 11.1-11.7 (1H, m)

[1249] The compound of Example 734 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.81-2.20, 2.6-4.0, 4.2-4.6 (total 33H, m), 6.8-8.0 (total 7H, m), 10.8-11.3 (1H, m)

[1250] The compound of Example 735 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.1-2.2, 2.6-4.1, 4.3-4.6 (total 26H, m), 6.8-7.9 [total 12H, m, 7.63 (s), 7.93 (s)], 10.8-11.4 (1H, m)

[1251] The compound of Example 736 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.99-2.20, 2.63-3.91, 4.81-5.08 [total 23H, m,1.12 (d, J=6.77 Hz)], 6.48 (1H, dd, J=8.6 Hz, J=8.5 Hz), 6.71-7.48 (6H, m)

[1252] The compound of Example 740 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-1.80,1.80-2.25, 2.35-2.60, 2.60-3.15, 3.25-3.55, 4.35-4.65, 4.85-5.05 [total 15H, m, 2.46 (s), 4.43 (s), 4.48 (s)]6.52-6.65, 6.78-6.95, 7.12-7.55 (total 11H, m)

[1253] The compound of Example 744 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.32-2.26, 2.45-2.65, 2.65-3.30, 4.85-5.12 [total 11H, m, 2.53 (s)], 6.65-6.75, 6.75-7.06, 7.06-7.54, 7.54-7.96, 8.58-8.76 (total 11H, m)

[1254] The compound of Example 745 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.0-2.2, 2.7-4.8 (total 28H, m), 6.15-7.35 (11H, m), 10.3-10.95 (1H, m)

[1255] The compound of Example 747 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-1.00, 1.15-2.35, 2.35-4.27, 4.45-4.80 [total 32H, m, 3.38 (s)], 6.75-7.55 (7H, m), 12.6-13.4 (1H, br)

[1256] The compound of Example 748 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.66-1.10, 1.10-1.49, 1.49-2.34, 2.34-4.23, 4.35-4.80 (total 38H, m), 6.73-7.55 (7H, m), 12.6-13.5 (1H, br)

[1257] The compound of Example 749 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-0.96, 0.96-2.22, 2.22-4.30, 4.30-4.83 [total 27H, m, 4.58 (s), 2.49 (s)], 6.48-7.53 (11H, m), 12.75-13.45 (1H, br)

[1258] The compound of Example 751 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.78-1.05, 1.15-4.30, 4.42-4.75 [total 33H, m, 0.93, 0.99 and 2.33 (each s)], 6.68-7.89 (8H, m)

[1259] The compound of Example 752 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.52 (3H, d, J=6.6 Hz), 0.97 (3H, d, J=6.6 Hz), 1.10-2.20, 2.20-3.20, 3.35-4.15 [total 13H, m, 2.62 (s)], 6.35-6.55, 7.00-7.60, 7.60-8.05 (total 10H, m), 8.65-8.80 (1H, m)

[1260] The compound of Example 753 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.25-2.45, 2.45-4.30, 4.30-4.90 (total 23H, m), 6.45-8.55 (total 11H, m), 8.75-9.00 (1H, m)

[1261] The compound of Example 756 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.7-0.95, 0.95-2.25, 2.60-4.20, 4.20-4.55 [total 34H, m, 0.8 (d, J=6.6 Hz), 2.66 (s)], 6.75-7.95, 8.29, 8.57 [total 8H, m, 7.62, 7.83, 8.29, 8.57 each (s)]

[1262] The compound of Example 759 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.09-2.19 [12H, m, 1.25 (t, J=7.2 Hz)], 2.28-3.67, 4.24-4.57, 4.68-4.98 [total 10H, m, 2.41 (s)], 6.68-7.81 (11H, m), 10.26-10.64 (1H, m)

[1263] The compound of Example 764 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.64-2.12 [11H, m, 0.75, 0.89 (each d, each J=6.5 Hz)], 2.12-5.05 [21H, m, 2.33 (s)], 6.37-7.52 (7H, m), 10.92-11.43 (1H, m)

[1264] The compound of Example 765 ¹H-NMR (200 MHz, CDCl₃+DMSO-d₆) δ ppm: 1.2-2.3 (4H, m), 2.5-3.4, 4.7-5.1, 5.3-5.6 (total 4H, each m), 6.5-7.5 (9H, m), 7.60 (1H, dd, J=7.5 Hz, J=7.5 Hz,), 7.95 (1H, d, J=7.5 Hz), 11.43 (1H, s)

[1265] The compound of Example 766 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.50 (3H, d, J=6.6 Hz), 0.76-1.40,1.50-2.18, 2.18-2.70, 2.70-4.18 [total 24H, m, 3.36 (s)], 6.28-6.42, 6.82-7.54 (total 8H, m)

[1266] The compound of Example 767 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.50 (3H, d, J=6.6 Hz), 0.69-1.05, 1.05-1.41, 1.41-2.19, 2.19-2.70, 2.95-4.15 (total 31H, m), 6.27-6.38, 6.75-7.52 (8H, m)

[1267] The compound of Example 768 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.55-0.65, 0.72-0.99, 1.20-1.44, 1.55-2.10, 2.10-2.90, 2.90-3.25, 3.25-4.10 (total 36H, m), 6.30-6.45, 6.75-6.94, 7.00-7.50 (total 8H, m)

[1268] The compound of Example 769 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-4.70, 4.89-5.12 [total 26H, m, 2.34 (s), 4.33 (t, J=5.4 Hz), 4.40 (t, J=5.3 Hz)], 6.72-7.70 (7H, m)

[1269] The compound of Example 770 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.61 (3H, d, J=6.6 Hz), 0.97 (3H, d, J=6.6 Hz), 1.15, 1.30, 1.55-2.15, 2.25-2.70, 2.90-3.20, 3.32-3.52, 3.60-3.95 (total 19H, m), 4.40-4.60 (4H, m), 6.20-6.40, 6.51-6.52, 6.82-7.55 (total 13H, m)

[1270] The compound of Example 771 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.82-2.25 [11H, m, 0.97 (d, J=6.6 Hz)], 2.29-4.98 [21H, m, 2.43 (s)], 6.49-7.79 (11H, m), 10.85-11.30 (1H, m)

[1271] The compound of Example 773 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.00-2.30 [7H, m, 1.28 (t, J=7.2 Hz)], 2.31-5.08 [21H, m, 2.43 (s), 3.76 (s)], 6.48-7.81 (11H, m), 10.81-11.31 (1H, m)

[1272] The compound of Example 774 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.01-2.38 (4H, m), 2.39-5.02 [24H, m, 2.43 (s), 3.76 (s), 3.81 (s)], 6.49-7.78 (11H, m), 10.47-11.08 (1H, m)

[1273] The compound of Example 775 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.01-2.28 [10H, m, 1.19 (t, J=7.1 Hz)], 2.29-5.02 [22H, m, 2.44 (s), 3.77 (s), 3.81 (s)], 6.49-7.81 (11H, m), 9.92-10.32 (1H, m)

[1274] The compound of Example 777 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.21-3.18, 3.58-3.85, 4.15-4.40, 4.82-5.15 [total 25H, m, 2.63 (t, J=5.73 Hz), 4.27 (t, J=5.8 Hz)], 6.41-7.01, 7.18-7.49, 7.75-7.92 [total 7H, m, 7.85 (d, J=8.5 Hz)]

[1275] The compound of Example 778 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.96 (6H, d, J=10.7 Hz), 1.21-4.11, 4.31-4.59, 5.01-5.22 [total 21H, m, 2.41 (s), 3.70 (s), 3.92 (d, J=6.6 Hz)], 6.49-7.67, 7.80-8.05 [total 8H, m, 7.92 (d, J=8.4 Hz)]

[1276] The compound of Example 779 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-1.86, 1.86-2.29, 2.40-2.63, 2.63-3.16, 3.32-3.52, 4.85-5.08 [total 11H, m, 2.52 (s), 2.57 (s)], 6.56-6.68, 6.82-7.56 (6H, m), 8.86, 8.97 (total 2H, each s), 9.17, 9.23 (total 1H, each s)

[1277] The compound of Example 780 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.38-1.66, 1.85-2.22, 2.62-3.16, 4.90-5.15 (8H, m), 3.71 (3H, s), 6.58-6.70 (1H, m), 6.70-6.82 (1H, m), 6.82-7.00 (2H, m), 7.12-7.31 (2H, m), 7.50-7.80 (3H, m), 7.60-7.70 (1H, m)

[1278] The compound of Example 781 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.20, 2.65-3.15, 4.92-5.13 (total 8H, m), 3.67 (3H, s), 6.55-6.84 (2H, m), 6.84-7.00 (2H, m), 7.00-7.19 (1H, m), 7.19-7.34 (2H, m), 7.73-7.85 (1H, m), 8.48-8.60 (1H, m), 8.60-8.72 (1H, m)

[1279] The compound of Example 783 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-4.68, 5.00-5.19 [total 27H, m, 2.36 (s), 3.75 (s)], 6.48-7.59 (7H, m)

[1280] The compound of Example 784 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-2.21, 2.55-3.19, 3.41-3.55, 3.65-3.80, 3.95-4.23, 4.89-5.12 [total 31H, m, 1.45 (s), 3.73 (s)], 6.51-6.74, 6.82-6.95, 7.19-7.35, 7.80-7.90 [total 7H, m, 7.84 (d, J=8.4 Hz)]

[1281] The compound of Example 785 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.0-4.0, 4.0-5.2 (total 29H, m), 6.1-8.2 (total 11H, m)

[1282] The compound of Example 786 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.0-1.4, 1.4-4.0, 4.0-5.2 (total 33H, m), 6.15-6.35, 6.6-8.25 (total 7H, m), 12.4-13.4 (1H, m)

[1283] The compound of Example 787 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-1.6, 1.6-2.2, 2.6-3.75, 3.9-4.6 (total 28H, m), 6.5-7.6, 7.8-8.2 (total 12H, m), 10.8-11.2 (1H, m)

[1284] The compound of Example 788 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.25-4.0, 4.35-4.55, 5.0-5.20 [total 30H, m, 2.33 (s), 2.82 (s), 3.63 (s)], 6.55-7.55 [total 6H, m, 6.6 (d, J=6.6 Hz), 6.96 (d, J=6.6 Hz), 7.20 (d, J=6.6 Hz), 7.49 (s)]

[1285] The compound of Example 790 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-1.69, 1.78-2.26, 2.53-3.14, 3.30-3.81, 4.29-4.51, 4.90-5.18 [total 15H, m, 2.98 (t, J=5.3 Hz), 4.39 (t, J=5.3 Hz), 3.72 (s)], 6.45-7.35, 7.65-7.92, 8.40-8.65 (total 11H, m)

[1286] The compound of Example 794 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-3.95, 4.41-4.63, 4.95-5.15 [total 28H, m, 1.49 (s), 1.58 (s), 2.38 (s)], 6.75-7.92 (7H, m)

[1287] The compound of Example 795 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-4.05, 4.45-4.70, 4.81-5.13 [total 27H, m, 2.40 (s), 1.25 (d, J=6.2 Hz), 1.31 (d, J=6.3 Hz)], 6.60-7.82 (8H, m)

[1288] The compound of Example 796 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.18, 2.18-4.20, 4.25-470, 4.90-5.15 [total 24H, m, 3.85 (s)], 6.55-7.15, 7.15-7.60, 7.70-8.10 (total 21H, m)

[1289] The compound of Example 801 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.03-2.04 (10H, m), 2.31-3.88, 4.29-4.54, 4.84-5.07 [total 19H, m, 2.43 (s), 3.77 (s)], 6.50-7.78 (11H, m), 8.44-8.69 (1H, m), 9.91-10.27 (1H, m)

[1290] The compound of Example 802 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.05-2.36 [total 10H, m, 1.18 (t, J=7.0 Hz)], 2.48-4.54, 4.79-5.21 [total 19H, m, 3.60 (s)], 6.67-7.62 (11H, m), 10.04-10.39 (1H, m)

[1291] The compound of Example 803 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.05-2.10 (10H, m), 2.39-3.94, 4.18-4.49, 4.88-5.12 [total 16H, m, 3.58 (s)], 6.69-7.70 (11H, m), 8.34-8.71 (1H, m), 10.00-10.34 (1H, m)

[1292] The compound of Example 804 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.00-2.28 [10H, m, 1.23 (t, J=7.2 Hz)], 2.42-4.13, 4.26-4.52, 4.69-4.91 (total 19H, m), 6.76-7.85 (11H, m), 10.09-10.48, 11.10-11.26 (total 1H, m)

[1293] The compound of Example 805 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.99-2.06 [10H, m, 1.20 (t, J=7.0 Hz)], 2.38-4.08, 4.25-4.52, 4.72-4.92 (total 16H, m), 6.78-7.84 (11H, m), 8.43-8.68 (1H, m), 10.09-10.45 (1H, m)

[1294] The compound of Example 806 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.03-2.11 (4H, m), 2.34 (3H, s), 2.44-4.79, 4.88-5.10 (total 16H, m), 6.12-8.03 (11H, m), 11.08-11.55 (1H, m)

[1295] The compound of Example 807 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.03-2.13 (10H, m), 2.22-3.83, 4.17-4.48, 4.88-5.10 (total 16H, m, 2.35 (s)], 6.58-7.90 (11H, m), 8.39-8.81 (1H, m), 10.20-10.65 (1H, m)

[1296] The compound of Example 808 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.10-2.28 (4H, m), 2.52-4.68, 4.87-5.10 [total 22H, m, 3.51 (s), 3.65 (s)], 6.11-6.29, 6.42-7.65 (total 10H, m), 11.07-11.48 (1H, brs)

[1297] The compound of Example 809 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.95-2.26 (10H, m), 2.38-4.08, 4.20-4.52, 4.78-5.08 [total 19H, m, 3.58 (s), 3.75 (s)], 6.62-7.62 (10H, m), 8.36-8.68 (1H, m), 9.82-10.20 (1H, m)

[1298] The compound of Example 810 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.07-2.29 (4H, m), 2.30-4.78, 4.87-5.10 [total 22H, m, 3.51 (s), 3.65 (s)], 6.11-6.29, 6.42-7.63 (total 10H, m), 11.13-11.58 (1H, brs)

[1299] The compound of Example 811 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.03-2.30 (10H, m), 2.40-4.00, 4.18-4.76, 4.83-5.08 [total 19H, m, 3.58 (s), 3.75 (s)], 6.63-7.64 (10H, m), 8.34-8.71 (1H, m), 9.92-10.39 (1H, m)

[1300] The compound of Example 812 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.05-2.09 (4H, m), 2.30 (3H, s), 2.58-4.71, 4.88-5.08 [total 19H, m, 3.57 (s)], 6.12-7.68 (10H, m), 11.00-11.50 (1H, brs)

[1301] The compound of Example 813 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.96-2.19 [10H, m, 1.19 (t, J=7.0 Hz)], 2.31 (3H, s), 2.55-4.69, 4.82-5.08 [total 19H, m, 3.59 (s)], 6.14-7.63 (10H, m), 10.19-10.52, 11.00-11.30 (total 1H, m)

[1302] The compound of Example 814 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.30, 2.50-3.85, 4.48-4.67, 5.06-5.24 [total 15H, m, 2.56 (a), 3.72 (s)], 6.50-6.72 (1H, m), 6.72-7.95 (9H, m), 8.75 (1H, m)

[1303] The compound of Example 820 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-1.00, 1.00-2.20, 2.60-3.05, 3.05-3.43, 3.43-3.96, 4.45-4.62 [total 24H, m, 1.59 (s), 3.19 (s), 3.69(s)], 6.80-7.50 (7H, m)

[1304] The compound of Example 821 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.70-1.00, 1.10-2.20, 2.60-3.95, 4.45-4.65, 5.02-5.15 (total 21H, m), 6.80-7.55 (7H, m)

[1305] The compound of Example 822 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.60-1.05, 1.15-2.20, 2.60-3.05, 3.15-3.95, 4.45-4.60, 5.02-5.15 (total 30H, m), 6.72-7.60 (7H, m)

[1306] The compound of Example 823 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.63-1.00, 1.10-2.20, 2.60-3.95, 4.45-4.60, 5.00-5.20 (total 27H, m), 6.68-7.58 (7H, m)

[1307] The compound of Example 825 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.20, 2.35-2.60, 2.60-3.85, 4.25-4.65 (total 16H, m), 6.40-6.66 (1H, m), 6.70-7.55 (11H, m)

[1308] The compound of Example 826 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.25, 2.25-3.26, 3.26-3.90, 4.50-4.70 [total 2H, m, 2.61 (s)], 6.72-6.85 (1H, m), 6.85-6.97 (1H, m), 7.00-7.35 (3H, m), 7.35-7.45 (1H, d, J=8.2 Hz), 7.56-7.78 (2H, m), 7.85-8.12 (2H, m), 8.20-8.38 (1H, m), 8.70-8.80 (1H, m)

[1309] The compound of Example 827 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-2.4 (4H, m), 2.7-3.8, 4.4-4.7, 4.9-5.2 (total 5H, each m), 6.8-8.4(7H, m)

[1310] The compound of Example 828 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-2.30 (4H, m), 2.35-4.08, 4.40-4.64, 4.92-5.20 [total 13H, m, 2.52 (s), 3.72 (s), 5.08 (s)], 6.48-7.62 (16H, m)

[1311] The compound of Example 829 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-2.26, 2.32-3.69, 4.81-5.20 [total 13H, m, 2.49 (s), 5.07 (s)], 6.57-7.63 (16H, m)

[1312] The compound of Example 833 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.86, 0.93, 1.07, 1.15-2.15, 2.60-3.80, 4.35-4.60 [total 23H, m, 0.86 (d, J=6.6 Hz), 0.93 (d, J=6.6 Hz), 1.07 (t, J=7 Hz) 6.75-7.60 (total 7H, m), 8.25-8.80 (1H, m)

[1313] The compound of Example 834 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.15, 2.55-3.85, 4.35-4.55, 4.67 [total 15H, m, 4.67 (s)], 6.70-7.40, 7.44, 7.50-7.90 [total 12H, m, 7.44 (s)]

[1314] The compound of Example 835 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.35-2.24, 2.39-2.62, 2.63-3.18, 3.29-3.99, 4.06-4.63, 4.83-5.11 [total 15H, m, 2.49 (s), 3.81 (t, J=6.0 Hz)], 6.58-7.62 (11H, m)

[1315] The compound of Example 836 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.67-1.03, 1.05-2.54, 2.55-4.28, 4.41-4.63, 5.00-5.21 [total 24H, m, 0.78 (d, J=6.6 Hz), 0.92 (d, J=6.6 Hz), 2.28 (d, J=7.2 Hz), 2.43 (s), 3.71 (s)], 6.40-7.41 (7H, m)

[1316] The compound of Example 840 ¹H-NMR (200 MHz,DMSO-d₆) δ ppm: 0.65-0.98, 1.04-2.12, 2.13-3.70, 4.26-4.51, 4.81-5.02 [total 21H, m, 0.75 (d, J=6.5 Hz), 0.89 (d, J=6.5 Hz), 2.27 (d, J=7.1 Hz), 2.33 (s)], 6.38-7.42 (7H, m), 12.14-12.42 (1H, m)

[1317] The compound of Example 844 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.13-4.01, 4.48-4.72 [total 23H, m, 2.33 (s)], 5.10 (2H, d, J=10.3 Hz), 6.43-7.64 (16H, m)

[1318] The compound of Example 845 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.09-4.20, 4.50-4.70, 4.96-5.16 [total 23H, m, 2.36 (s)], 6.41-7.48 (12H, m)

[1319] The compound of Example 849 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-2.2 (4.5H, m), 2.7-3.0 [total 5H, m, 2.83 (s)], 3.1-3.3, 3.3-3.5, 3.6-3.85, 4.35-4.5, 5.05-5.35 [total 12.5H, m, 3.40 (t, J=7.4 Hz), 3.67 (s), 3.77 (s)], 6.62 (1H, d, J=8.1 Hz), 6.82 (1H, d, J=8.1 Hz), 6.9-7.4 (4H, m)

[1320] The compound of Example 850 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.95 (6H, d, J=6.2 Hz), 1.25-2.15, 2.7-3.3, 3.67, 3.72, 4.35-4.65, 5.10-5.4 [total 19H, m, 3.67 (s), 3.72 (s)], 6.26, 6.64, 6.73-6.78, 6.96, 7.12-7.4 [total 6H, m, 6.26 (d, J=8.1 Hz)], 6.64 (d, J=8.1 Hz), 6.96 (dd, J=8.1 Hz, J=2.2 Hz)]

[1321] The compound of Example 851 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.2-2.2, 2.7-3.05, 3.15-3.3, 3.4-4.0, 4.4-4.55, 4.6-4.8, 5.05-5.26 [total 20H, m, 3.69 (s), 3.71 (s)], 6.60-7.45 [total 6H, m, 6.63 (d, J=8.1 Hz), 6.85 (d, J=8.1 Hz)]

[1322] The compound of Example 852 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.17-2.30 (4H, m), 2.57-3.03, 3.09-3.33, 3.43-3.92, 4.38-4.63, 5.08-5.28 [total 10H, m, 3.62 (s), 3.70 (s)], 6.53-7.43 (10H, m)

[1323] The compound of Example 853 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-2.30 (4H, m), 2.60-3.05, 3.10-3.37, 3.46-4.33, 4.38-4.62, 5.08-5.29 [total 10H, m, 3.67 (s), 3.71 (s), 3.81 (s)], 6.52-7.46 (10H, m)

[1324] The compound of Example 854 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.19-2.46 [7H, m, 2.37 (s)], 2.58-3.04, 3.05-4.26, 4.38-4.63, 5.06-5.28 [total 11H, m, 3.67 (s), 3.71 (s)], 6.54-7.48 (10H, m)

[1325] The compound of Example 855 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.20-2.28 (4H, m), 2.39 (3H, s), 2.57-3.10, 3.11-4.35, 4.40-4.63, 5.08-5.30 [total 8H, m, 3.75 (s)], 6.47-6.71, 6.81-7.78 (total 11H, m)

[1326] The compound of Example 856 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.12-2.19 (4H, m), 2.57-4.08, 4.20-4.66, 4.81-5.08 [total 11H, m, 3.52 (s), 3.65 (s)], 6.62-7.62 (10H, m), 12.36 (1H, s)

[1327] The compound of Example 857 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.10-2.19 (4H, m), 2.43-4.14, 4.20-4.71, 4.83-5.10 [total 11H, m, 3.59 (s), 3.75 (s)], 6.67-7.65 (10H, m), 12.20-12.57 (1H, brs)

[1328] The compound of Example 858 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.13-2.38 [7H, m, 2.31 (s)], 2.51-4.02, 4.19-4.75, 4.82-5.08 [total 8H, m, 3.59 (s)], 6.62-7.80 (10H, m), 12.20-12.58 (1H, brs)

[1329] The compound of Example 859 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.18-2.18 (4H, m), 2.34 (3H, s), 2.48-4.12, 4.20-4.80, 4.89-5.12 (total 5H, m), 6.61-7.88 (11H, m), 12.12-12.60 (1H, m)

[1330] The compound of Example 868 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.06-2.69, 2.98-4.26, 4.60-4.81 [total 33H, m, 2.32 (s), 2.39 (s)], 6.42-7.45 (7H, m)

[1331] The compound of Example 869 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.68-2.72, 3.01-4.25, 4.65-4.92 [total 25H, m, 2.32(s), 2.47(s), 3.82 (s)], 6.46-7.12 (11H, m)

[1332] The compound of Example 871 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.16-2.98, 3.42-3.91, 4.02-4.25, 4.60-4.88, 5.02-5.40 [total 19H, m, 2.35 (s), 4.79 (s)], 6.61-7.05, 7.13-7.94 (total 12H, m)

[1333] The compound of Example 870 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.93-2.98, 3.29-4.59, 4.69-5.31 [total 23H, m, 2.35 (s), 3.60 (t, J=5.50 Hz), 4.35 (t, J=5.3 Hz)], 6.69-7.70 (7H, m)

[1334] The compound of Example 841 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.85-2.22, 2.55-3.31, 3.41-3.80, 4.05-4.31, 4.41-4.62 [total 25H, m, 3.69 (s)], 6.71-7.70 (7H, m)

[1335] The compound of Example 842 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.82-1.03,1.15-2.20, 2.45-4.62 [total 22H, m, 0.93 (s)], 6.48-8.21 (8H, m)

[1336] The compound of Example 843 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-2.41, 2.56-4.65, 4.90-5.16 (total 15H, m), 6.52-7.61 (7H, m), 9.39-10.05 (1H, m)

[1337] The compound of Example 860 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.15-2.25, 2.50-3.03, 3.10-3.30, 3.48-3.91, 4.25-4.55, 5.05-5.28 [total 19H, m, 3.71 (s), 3.74 (s), 4.40 (t, J=5.9 Hz)], 6.42-7.42, 7.71-7.99 [total 7H, m, 6.58 (d, J=8.3 Hz), 7.86 (d, J=8.3 Hz)]

[1338] The compound of Example 861 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-2.21, 2.51-3.31, 3.45-4.10, 4.30-4.60, 5.03-5.31 [total 24H, m, 0.95 (d, J=6.7 Hz), 3.92 (d, J=7.2 Hz), 3.72 (s), 3.74 (s)], 6.42-7.41, 7.65-8.00 [total 7H, m, 6.58 (d, J=8.3 Hz), 7.88 (d, J=8.3 Hz)]

[1339] The compound of Example 862 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-2.31, 2.51-3.32, 3.42-4.09, 4.30-4.58, 5.05-5.21 [total 19H, m, 3.79 (s), 4.44 (t, J=7.8 Hz)], 6.49-7.42 [6H, m, (d, J=8.3 Hz)]

[1340] The compound of Example 863 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.88 (6H, d, J=6.7 Hz), 1.10-2.07, 2.52-4.45, 4.85-5.02 [total 15H, m, 3.63 (s), 3.98 (d, J=7.2 Hz)], 6.50-6.88, 6.98-7.29, 7.38-7.79, 8.28-8.49 [total 7H, m, 6.70 (d, J=8.3 Hz), 7.52 (d, J=8.3 Hz)]

[1341] The compound of Example 864 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 1.01-2.10, 2.39-4.51, 4.86-5.05 [total 13H, m, 3.67 (s)], 6.0-7.75 (6H, m), 9.99 (1H, s)

[1342] The compound of Example 865 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-2.21, 2.60-3.29, 3.41-3.90, 4.41-4.65, 4.82-5.20 [total 19H, m, 1.26 (d, J=6.4 Hz), 3.69 (s)], 6.53-7.80 [total 8H, m, 6.71 (s), 7.46 (s)]

[1343] The compound of Example 867 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.11-2.29, 2.68-3.92, 4.38-4.70, 5.01-5.19 [total 20H, m, 1.50 (s), 1.58 (s), 2.16 (s), 3.70 (s)], 6.78-7.90 [total 7H, m, 7.59 (d, J=2.1 Hz)]

[1344] The compound of Example 873 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.80-2.61, 2.88-3.72, 3.85-4.40, 4.62-5.01 [total 27H, m, 1.31 (t, J=7.0 Hz), 2.35 (s), 4.22 (q, J=7.1 Hz)], 6.41-7.49 (7H, m)

[1345] The compound of Example 874 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.18-1.48,1.68-2.62, 2.95-4.41, 4.71-5.05 [total 19H, m, 1.31 (t, J=7.1 Hz), 2.50 (s), 3.80 (s), 4.22 (q, J=6.8 Hz)], 6.45-7.65 (total 11H, m)

[1346] The compound of Example 875 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.10-2.62, 2.90-3.70, 3.85-4.21, 4.65-4.95 [total 22H, m, 2.35 (s)], 6.35-7.45 (7H, m)

[1347] The compound of Example 876 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.69-2.62, 2.81-4.28, 4.65-4.98 [total 14H, m, 2.43 (s), 3.80 (s)], 6.41-7.62 [11H, m, 7.38 (d, J=9.2 Hz)]

[1348] The compound of Example 877 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.53 (9H, s), 1.71-2.24, 2.50-2.91, 3.40-4.45, 4.61-5.10 [total 12H, m, 3.59 (t, J=6.3 Hz), 4.28 (t, J=6.0Hz)], 6.65-7.80, 8.55-8.68 (total 8H, m)

[1349] The compound of Example 878 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.53 (9H, s), 2.09-2.31, 2.52-2.82, 3.55-4.51, 4.62-5.09 [total 12H, m, 2.17 (t, J=5.1 Hz), 4.37 (t, J=5.5 Hz)], 6.89-7.71 (7H, m)

[1350] The compound of Example 879 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 2.05-2.90, 3.46-5.10 [total 12H, m, 3.60 (t, J=5.8 Hz), 4.38 (t, J=5.3 Hz)], 6.81-7.71 (7H, m), 10.1-10.6 (1H, m)

[1351] The compound of Example 880 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.51-2.88, 3.10-5.15 [total 6H, m, 4.94 (s)], 6.70-7.35, 7.45-7.85, 7.92-8.28, 8.55-8.65 (total 13H, m)

[1352] The compound of Example 881 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.12-1.41, 2.51-2.86, 3.69-4.01, 4.10-4.48, 4.62-4.98 [total 13H, m, 1.29 (t, J=4.0 Hz), 4.69 (s)], 6.65-7.10, 7.19-7.92 [total 12H, m, 7.73 (d, J=8.8 Hz), 7.84 (d, J=7.0 Hz)]

[1353] The compound of Example 882 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 2.30-2.76, 3.56-3.96, 4.27-4.80 (total 4H, m), 4.94 (2H, s), 6.71-7.90 (8H, m)

[1354] The compound of Example 883 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.60-2.09, 2.28-4.32, 4.60-5.10 (total 10H, m), 6.41-8.25, 8.41-8.90 [total 13H, m, 8.12 (d, J=7.4 Hz)]

[1355] The compound of Example 884 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.05-1.49,2.25-4.99 [total 15H, m, 1.31 (t, J=7.1 Hz)], 6.60-7.90, 8.00-8.28 [total 12H, m, 8.12 (d, J=7.7 Hz)]

[1356] The compound of Example 885 ¹H-NMR (200 MHz, DMSO-d₆) δ ppm: 0.85-4.70, 4.88-6.20 (total 11H m), 6.51-8.62 [total 12H, m, 7.94 (d, J=7.2 Hz)]

[1357] The compound of Example 866 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.85-2.18, 2.45-3.90, 4.29-4.60, 4.78-5.18 [total 16H, m, 1.28 (d, J=7.2 Hz)], 6.40-7.81 (8H, m), 7.90-9.60 (1H, m)

[1358] The compound of Example 789 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.4-1.4, 1.4-2.4, 2.4-2.85, 2.85-3.3, 3.3-5.0, 5.0-5.8 (total 29H, m), 6.29, 6.5-7.5 [total 6H, m, 6.29 (d, J=8.4 Hz)]

[1359] The compound of Example 792 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 0.75-0.98, 1.21-2.20, 2.42-4.19, 4.85-5.19 [total 25H, m, 2.60 (s), 3.73 (s)], 6.45-6.75, 6.80-7.00 (total 5H, m), 7.23 (1H, d, J=2.4 Hz), 7.81 (1H, d, J=6.6 Hz)

[1360] The compound of Example 797 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.03-1.40, 1.50-2.23, 2.23-2.58, 2.53-4.05, 4.05-4.30, 4.52-4.73 [total 24H, m, 1.60 (s), 2.13 (s)], 6.55-7.05, 7.05-7.50 (total 20H, m)

[1361] The compound of Example 798 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.30-2.20, 2.62-3.18, 4.85-5.05 (total 8H, m), 3.68 (3H, brs), 6.67-6.90, 7.00-7.50 (total 7H, m), 7.75-7.85 (1H, m), 8.50-8.65 (1H, m), 8.65-8.85 (1H, m)

[1362] The compound of Example 799 ¹H-NMR (200 MHz, CDCl₃) δ ppm: 1.30-1.80, 1.80-2.20, 2.62-2.93, 2.93-3.20, 4.82-5.03 (total 8H, m), 3.71 (3H, s), 6.69-6.85 (2H, m), 7.10-7.48 (5H, m), 7.60-7.80 (2H, m), 8.60-8.70 (1H, m)

[1363] Pharmacological Test

[1364] Experiment 1: V₁ Receptor Binding Assay

[1365] Using rat liver plasma membrane preparations prepared according to Ichihara's method [cf: Akira Ichihara, J. Bio. Chem., 258, 9283 (1983)], the plasma membrane (50000 dpm, 2×10⁻¹⁰ M) of [³H]-Arg-vasopressin and a test compound (60 μg, 10⁻⁸ to 10⁻⁴ M) are incubated at 37° C for 10 minutes in 100 mM Tris-HCl buffer (pH 8.0) (250 μl) containing 5 mM MgCl₂, 1 mM EDTA and 0.1% BSA. After incubation, the mixture is filtered three times using the glass filter (GF/F) so as to separate the membrane preparation binding with vasopressin and then washed with the buffer (5 ml). This glass filter is taken cut and mixed with liquid scintillation cocktail. The amount of [³H]-vasopressin binding with the membrane is measured by liquid scintillation counter and the rate of the inhibitory effect of the test compound is estimated according to the following equation.

Rate of the inhibitory effect (%)=100−[(C ₁ −B ₁)/(C ₀ −B ₁)]×100

[1366] C₁: The amount of [³H]-vasopressin binding with the membrane in the presence of the test compound (known amount)

[1367] C₀: The amount of [³H]-vasopressin binding with the membrane in the absence of the test compound

[1368] B₁: The amount of [³H]-vasopressin binding with the membrane in the presence of the excess amount of vasopressin (10⁻⁶ M)

[1369] The results are expressed as IC₅₀ value, which is the concentration of the test compound required to achieve the inhibitory effect in the rate of 50%.

[1370] The results are shown in the following Table.

[1371] Experiment 2: V₂ Receptor Binding Assay

[1372] Using rat kidney plasma membrane preparations prepared according to OHechter's method [cf: J. Bio. Chem., 253, 3211 (1978)], the plasma membrane (100000 dpm, 4×10⁻¹⁰ M) of [³H]-Arg-vasopressin and a test compound (0.6 mg, 10⁻¹⁰ to 10⁻⁵ M) are incubated at 4° C. for 3 hours in 100 mM Tris-HCl buffer (pH 8.0) (250 μl) containing 5 mM MgCl₂, 1 mM EDTA and 0.1% BSA. After incubation, the mixture is filtered using the glass filter (GF/F) so as to separate the membrane preparation binding with vasopressin and then washed twice with the buffer (each 5 ml). This glass filter is taken out and mixed with liquid scintillation cocktail. The amount of [³H]-vasopressin binding with the membrane is measured by liquid scintillation counter and the rate of the inhibitory effect of the test compound is estimated according to the following equation.

Rate of the inhibitory effect (%)=100−[(C ₁ −B ₁)/(C ₀ −B ₁)]×100

[1373] C₁: The amount of [³H]-vasopressin binding with the membrane in the presence of the test compound (known amount)

[1374] C₀: The amount of [³H]-vasopressin binding with the membrane in the absence of the test compound

[1375] B₁: The amount of [³H]-vasopressin binding with the membrane in the presence of the excess amount of vasopressin (10⁻⁶ M)

[1376] The results are expressed as IC₅₀ value, which is the concentration of the test compound required to achieve the inhibitory effect in the rate of 50%.

[1377] The results are shown in the following Table. IC₅₀ (μM) in V₁ IC₅₀ (μM) in V₂ receptor Test compound receptor binding assay binding assay Compound of Ex. 29 0.021 0.15

[1378] Experiment 3: Anti-vasopressor Activity in vivo

[1379] The spinal cord of mal SD rat (weighing 300-400 g) is broken to give a pith rat. The blood pressure of the pith rat is measured through the cannula inserted into the femoral artery thereof by using a pressure transducer. The test compound and Arg-vasopressin are administered to the pith rat through the cannula inserted into the femoral vein. Anti-vasopressor activity of the test compound in vivo is determined according to the following equation.

Anti-vasopressor activity (%)=P/P ₀×100

[1380] P₀: The increase of diastolic pressure when Arg-vasopressin (30 mU/kg) is administered intravenously.

[1381] P: The increase of diastolic pressure when Arg-vasopressin (30 mU/kg) is administered intravenously 3 minutes after the intravenous administration of the test compound.

[1382] The results are expressed as ED₅₀ value, which is the dose of the test compound required to reduce the increase of diastolic pressure caused by the intravenous administration of Arg-vasopressin (30 mU/kg) to 50% of its control value: P₀.

[1383] The results are shown in the following Table. Test compound ED₅₀ (mg/kg) Compound of Ex. 29 1.0 Compound of Ex. 70 2.8

[1384] Experiment 4: Anti-antidiuretic Activity (Effect on Endogenous ADH)

[1385] A test compound or a solvent (dimethylformamide) is administered into a caudal vein of untreated, unrestrained SD rats (male, weight: 300-350 g) and the amount of urine, which is spontaneously excreted for a period of two hours thereafter, is collected and measured by using a metabolic gauge. During this measurement, the rats are allowed to take water and feed freely.

[1386] In the group treated by administration of the compound of Example 493 at a dose of 10 mg/kg, the amount of urine, which is excreted for two hours from the administration of the test compound, is four times larger than that in the control group.

[1387] Experiment 5: Antidiuretic Activity

[1388] A test compound is dissolved in polyethylene glycol 400 or water, or suspended in 5% gum arabic solution to give a test compound solution.

[1389] The test compound solution is orally and forcibly administered to untreated, unrestrained Brattleburo rats, which hereditarily lack vasopressin. In the control group, a solvent is administered instead of a test compound solution. After the administration, the rats are put into a metabolic gauge, and the spontaneously excreted urine is collected for two hours, and the amount thereof is measured. During this measurement, the rats are allowed to take water and feed freely.

[1390] In the group treated by oral administration of Example 562 at a dose of 1 mg/kg, the amount of the urine, which is excreted for two hours after the administration of the test compound, is one fifth of that in the control group. 

1. A benzoheterocyclic derivative of the following formula [1]:

wherein G is a group of the formula:

or a group of the formula:

R¹ is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group, an amino group having optionally a lower alkyl substituent, a carboxy-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, or an aminocarbonyl-lower alkoxy group having optionally a lower alkyl substituent, R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different, and each a hydrogen atom, a lower alkyl group having optionally a hydroxy substituent or a benzoyl group having optionally a halogen substituent on the phenyl ring); a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group; a lower alkanoyl group; or a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which m and u are each 0 or 1, but both m and u should not be simultaneously 0, A is a lower alkylene group, R⁶ and R⁷ are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, or R² and R³ may bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylylene group, or a phenyl-substituted lower alkylidene group, R is a pyridylcarbonyl group which may optionally have a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group; a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; a cycloalkylcarbonyl group; or a group of the formula:

 (in which p is 1 or 2, R⁸ is a hydrogen atom, a lower alkyl group, a hydroxy group, an amino group having optionally a lower alkanoyl substituent, a nitro group, a halogen atom or a lower alkoxy group, R⁹ is a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ is a hydrogen atom, a lower alkyl group, or a lower alkanoyl group having optionally a halogen substituent, R¹¹ is a lower alkyl group, a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the lower alkanoyl moiety, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a lower alkoxycarbonyl group having optionally a halogen substituent, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a phenoxy-lower alkoxycarbonyl group, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a phenyl-lower alkoxycarbonyl group, a group of the formula:

 a tetrahydroisoquinolylcarbonyl group, a benzoyl-lower alkyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a lower alkylsulfonyl group, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a phenyl-lower alkenylcarbonyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, or R¹⁰ and R¹¹ may bind together with the nitrogen atom to which they bond to form an isoindoline ring); a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a cycloalkyl group; a lower alkyl group; a lower alkylthio group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, and an amino-substituted lower alkoxy group haying optionally a lower alkyl substituent; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a saturated or unsaturated 5- to 11-membered heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: —(A)_(m)—CHR¹²R¹³ (in which A is the same as defined above, R¹² is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R¹³ is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1)), X is a methylene group, a single bond, a group of the formula: ═CH— or a group of the formula: —NR¹⁴— (in which R¹⁴ is a hydrogen atom, a lower alkyl group or a lower alkanoyl group), Y is a group of the formula: —NR^(A) (in which R^(A) is a hydrogen atom, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: —ACONR^(B)R^(C) (in which R^(B) and R^(C) are the same or different and each a hydrogen atom or a lower alkyl group, or R^(B) and R^(C) may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group)), provided that when R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different and each a hydrogen atom, a lower alkyl group or a benzoyl group), a hydrogen atom, a hydroxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group, a lower alkoxy group, a lower alkanoyloxy-substituted lower alkyl group, a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (m and u are the same as defined above, R⁶ and R⁷ are the same or different and each a hydrogen atom or a lower alkyl group, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group), or an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; or R² and R³ may bind together to form an oxo group or a lower alkylidene group; and when R is a group of the formula:

 and R⁸ in said group is a hydrogen atom, a lower alkyl group, a hydroxy group, a halogen atom, a lower alkoxy group or an amino group, then R⁹ should not be a hydrogen atom, a phenyl-lower alkoxycarbonyl group, nor a group of the formula: —NR¹⁰R¹¹ (R¹¹ is a lower alkanoyl group or a phenoxy-lower alkanoyl group having optionally 1 to 3 substituents selected from a lower alkyl group and a lower alkoxy group on the phenyl ring), or when R¹ is a hydrogen atom, R² is a hydrogen atom, an amino group, a mono-lower alkylamino group or a di-lower alkylamino group, or R² and R³ may bind together to form an oxo group, then R⁹ should not be a phenyl group having optionally a substituent selected from a hydroxy group, a lower alkyl group, a lower alkoxy group and a lower alkanoyloxy group on the phenyl ring, or when R⁹ is a group of the formula:

 (n is 1 or 2), and G is a group of the formula:

 (R² and R³ are the same as defined above), then X should not be a methylene group nor a group of the formula: ═CH—, or when one of R¹⁰ and R¹¹ is a hydrogen atom, the other should not be a lower alkyl group, or when R¹ and R² are simultaneously a hydrogen atom, then R should not be unsubstituted pyridylcarbonyl group, unsubstituted thienylcarbonyl group, unsubstituted thiazolylcarbonyl group, nor a cycloalkylcarbonyl group, or when R³ is a hydrogen atom, R² is a hydrogen atom, an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent, a lower alkoxycarbonyl-substituted lower alkoxy group, a hydroxy group, a lower alkoxy group, a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which R⁶ and R⁷ are the same or different and each a hydrogen atom or a lower alkyl group, m is 1, u is 0 or 1) or a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different and each a hydrogen atom or a lower alkyl group), or R² and R³ may bind together to form an oxo group or a lower alkylidene group, then R⁹ should not be a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ is a lower alkyl group, R¹¹ is a lower alkyl group), a hydrogen atom, a lower alkylthio group, a lower alkoxy group nor a lower alkyl group, or a pharmaceutically acceptable salt thereof.
 2. The compound according to claim 1, wherein G is a group of the formula:

(in which R² and R³ are the same as defined in claim 1, and X is a methylene group), or a pharmaceutically acceptable salt thereof.
 3. The compound according to claim 1, wherein G is a group of the formula:

(in which R² and R³ are the same as defined in claim 1, and X is a single bond), or a pharmaceutically acceptable salt thereof.
 4. The compound according to claim 1, wherein G is a group of the formula:

(in which R² and R³ are the same as defined in claim 1, and X is a group of the formula: ═CH—), or a pharmaceutically acceptable salt thereof.
 5. The compound according to claim 1, wherein G is a group of the formula:

(in which R² and R³ are the same as defined in claim 1, and X is a group of the formula: —NR¹⁴ (in which R¹⁴ is the same as defined in claim 1)), or a pharmaceutically acceptable salt thereof.
 6. The compound according to claim 1, wherein G is a group of the formula:

(in which R², R3 and Y are the same as defined in claim 1), or a pharmaceutically acceptable salt thereof.
 7. The compound according to claim 2, wherein R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9l-oxofluorenyl group, a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; or a cycloalkylcarbonyl group, or a pharmaceutically acceptable salt thereof.
 8. The compound according to claim 2, wherein R is a group of the formula:

wherein R⁸, R⁹ and p are the same as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 9. The compound according to claim 3, wherein R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group, a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; or a cycloalkylcarbonyl group, or a pharmaceutically acceptable salt thereof.
 10. The compound according to claim 3, wherein R is a group of the formula:

wherein R⁸, R⁹ and p are the same as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 11. The compound according to claim 4, wherein R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group, a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; or a cycloalkylcarbonyl group, or a pharmaceutically acceptable salt thereof.
 12. The compound according to claim 4, wherein R is a group of the formula:

wherein R⁸, R⁹ and p are the same as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 13. The compound according to claim 5, wherein R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group, a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; or a cycloalkylcarbonyl group, or a pharmaceutically acceptable salt thereof.
 14. The compound according to claim 5, wherein R is a group of the formula:

wherein R⁸, R⁹ and p are the same as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 15. The compound according to claim 6, wherein R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group, a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; or a cycloalkylcarbonyl group, or a pharmaceutically acceptable salt thereof.
 16. The compound according to claim 6, wherein R is a group of the formula:

wherein R⁸, R⁹ and p are the same as defined in claim 1, or a pharmaceutically acceptable salt thereof.
 17. The compound according to claim 8, wherein R⁹ is a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ and R¹¹ are the same as defined in claim 1), or a pharmaceutically acceptable salt thereof.
 18. The compound according to claim 8, wherein R⁹ is a cycloalkyl group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group,a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group and an amino-lower alkoxy group having optionally a lower alkyl substituent on the phenyl ring, or a pharmaceutically acceptable salt thereof.
 19. The compound according to claim 8, wherein R⁹ is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group, or a pharmaceutically acceptable salt thereof.
 20. The compound according to claim 8, wherein R⁹ is a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a lower alkyl group; a lower alkylthio group; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: —(A)_(m)—CHR¹²R¹³ (in which A is a lower alkylene group, R¹² is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R¹³ is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1), or a pharmaceutically acceptable salt thereof.
 21. The compound according to claim 14, wherein R⁹ is a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ and R¹¹ are the same as defined in claim 1), or a pharmaceutically acceptable salt thereof.
 22. The compound according to claim 14, wherein R⁹ is a cycloalkyl group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group,a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group and an amino-lower alkoxy group having optionally a lower alkyl substituent on the phenyl ring, or a pharmaceutically acceptable salt thereof.
 23. The compound according to claim 14, wherein R⁹ is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group, or a pharmaceutically acceptable salt thereof.
 24. The compound according to claim 14, wherein R⁹ is a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a lower alkyl group; a lower alkylthio group; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: —(A)_(m)—CHR¹²R¹³ (in which A is a lower alkylene group, R¹² is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R¹³ is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1), or a pharmaceutically acceptable salt thereof.
 25. The compound according to claim 16, wherein R⁹ is a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ and R¹¹ are the same as defined in claim 1), or a pharmaceutically acceptable salt thereof.
 26. The compound according to claim 16, wherein R⁹ is a cyclolakyl group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group,a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group and an amino-lower alkoxy group having optionally a lower alkyl substituent on the phenyl ring, or a pharmaceutically acceptable salt thereof.
 27. The compound according to claim 16, wherein R⁹ is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group, or a pharmaceutically acceptable salt thereof.
 28. The compound according to claim 16, wherein R⁹ is a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a lower alkyl group; a lower alkylthio group; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: —(A)_(m)—CHR¹²R¹³ (in which A is a lower alkylene group, R¹² is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R¹³ is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1), or a pharmaceutically acceptable salt thereof.
 29. The compound according to claim 18, wherein R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same as defined in claim 1), R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 30. The compound according to claim 18, wherein R² is a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which R⁶, R⁷, m and u are the same as defined in claim 1), R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 31. The compound according to claim 18, wherein R² is a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group, or a lower alkanoyl group, and R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 32. The compound according to claim 18, wherein R³ is a hydroxy-substituted lower alkyl group, or a pharmaceutically acceptable salt thereof.
 33. The compound according to claim 18, wherein R² and R³ bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group, or a pharmaceutically acceptable salt thereof.
 34. The compound according to claim 22, wherein R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same as defined in claim 1), R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 35. The compound according to claim 22, wherein R² is a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which R⁶, R⁷, A, m and u are the same as defined in claim 1), R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 36. The compound according to claim 22, wherein R² is a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group, or a lower alkanoyl group, and R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 37. The compound according to claim 22, wherein R³ is a hydroxy-substituted lower alkyl group, or a pharmaceutically acceptable salt thereof.
 38. The compound according to claim 22, wherein R² and R³ bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group, or a pharmaceutically acceptable salt thereof.
 39. The compound according to claim 26, wherein R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same as defined in claim 1), R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 40. The compound according to claim 26, wherein R² is a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which R⁶, R⁷, A, m and u are the same as defined in claim 1), R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 41. The compound according to claim 26, wherein R² is a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-subsutituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group, or a lower alkanoyl group, and R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 42. The compound according to claim 26, wherein R³ is a hydroxy-substituted lower alkyl group, or a pharmaceutically acceptable salt thereof.
 43. The compound according to claim 26, wherein R² and R³ bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group, or a pharmaceutically acceptable salt thereof.
 44. The compound according to claim 30, wherein m is 0, n is 1, R⁶ and R⁷ are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or a pharmaceutically acceptable salt thereof.
 45. The compound according to claim 30, wherein m is 0, n is 1, R⁶ and R⁷ bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group, or a pharmaceutically acceptable salt thereof.
 46. The compound according to claim 30, wherein both m and n are 1, or a pharmaceutically acceptable salt thereof.
 47. The compound according to claim 35, wherein m is 0, n is 1, R⁶ and R⁷ are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or a pharmaceutically acceptable salt thereof.
 48. The compound according to claim 35, wherein m is 0, n is 1, R⁶ and R⁷ bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group, or a pharmaceutically acceptable salt thereof.
 49. The compound according to claim 35, wherein both m and n are 1, or a pharmaceutically acceptable salt thereof.
 50. The compound according to claim 40, wherein m is 0, n is 1, R⁶ and R⁷ are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or a pharmaceutically acceptable salt thereof.
 51. The compound according to claim 40, wherein m is 0, n is 1, R⁶ and R⁷ bind together with the nitrogen atom to which they bond to form a 5- to 7- membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group, or a pharmaceutically acceptable salt thereof.
 52. The compound according to claim 40, wherein both m and n are 1, or a pharmaceutically acceptable salt thereof.
 53. The compound according to any one of claims 7 to 16, wherein R¹ is a hydrogen atom or a halogen atom, or a pharmaceutically acceptable salt thereof.
 54. The compound according to any one of claims 7 to 16, wherein R¹ is a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group, an amino group having optionally a lower alkyl substituent, a carboxy-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, or an aminocarbonyl-lower alkoxy group having optionally a lower alkyl substituent, or a pharmaceutically acceptable salt thereof.
 55. The compound according to claim 17, wherein R² is a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which R⁶, R⁷, A, m and n are the same as defined in claim 1), and R³ is a hydrogen atom, or a pharmaceutically acceptable salt thereof.
 56. 5-[(4-Methyl-1-piperazinyl)carbonylmethyl]-1-[4-(4-methoxyphenyl)-2-methylbenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine.
 57. 5-[(4-Methyl-1-piperazinyl)carbonylmethyl]-1-[4-cyclohexyl-2-methylbenzoyl]-2,3,4,5-tetrahydro-1 H-benzazepine.
 58. 5-Isopropylaminocarbonylmethyl-1-(2-chloro-4-dimethylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine.
 59. A vasopressin antagonist, which comprises as an active ingredient a benzoheterocyclic derivative as set forth in claim 1, or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier or diluent.
 60. An oxytocin antagonist, which comprises as an active ingredient a benzoheterocyclic compound as set forth in claim 1, or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier or diluent.
 61. A vasopressin agonist, which comprises as an active ingredient a benzoheterocyclic compound as set forth in claim 1, or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier or diluent.
 62. A method for antagonizing vasopressin, which comprises administering to a warm-blooded animal including a human being a therapeutically effective amount of a benzoheterocyclic derivative of the following formula [1]:

wherein G is a group of the formula:

or a group of the formula:

R¹ is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group, an amino group having optionally a lower alkyl substituent, a carboxy-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, or an aminocarbonyl-lower alkoxy group having optionally a lower alkyl substituent, R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different, and each a hydrogen atom, a lower alkyl group having optionally a hydroxy substituent or a benzoyl group having optionally a halogen substituent on the phenyl ring); a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group; a lower alkanoyl group; or a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which m and u are each 0 or 1, but both m and u should not be simultaneously 0, A is a lower alkylene group, R⁶ and R⁷ are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, or R² and R³ may bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group, R is a pyridylcarbonyl group which may optionally have a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group; a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; a cycloalkylcarbonyl group; or a group of the formula:

 (in which p is 1 or 2, R⁸ is a hydrogen atom, a lower alkyl group, a hydroxy group, an amino group having optionally a lower alkanoyl substituent, a nitro group, a halogen atom or a lower alkoxy group, R⁹ is a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ is a hydrogen atom, a lower alkyl group, or a lower alkanoyl group having optionally a halogen substituent, R¹¹ is a lower alkyl group, a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the lower alkanoyl moiety, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a lower alkoxycarbonyl group having optionally a halogen substituent, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a phenoxy-lower alkoxycarbonyl group, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a phenyl-lower alkoxycarbonyl group, a group of the formula:

 a tetrahydroisoquinolylcarbonyl group, a benzoyl-lower alkyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a lower alkylsulfonyl group, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a phenyl-lower alkenylcarbonyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, or R¹⁰ and R¹¹ may bind together with the nitrogen atom to which they bond to form an isoindoline ring); a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a cycloalkyl group; a lower alkyl group; a lower alkylthio group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a saturated or unsaturated 5- to 11-membered heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: —(A)_(m)—CHR¹²R¹³ (in which A is the same as defined above, R¹² is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R¹³ is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1)), X is a methylene group, a single bond, a group of the formula: ═CH— or a group of the formula: —NR¹⁴— (in which R¹⁴ is a hydrogen atom, a lower alkyl group or a lower alkanoyl group), Y is a group of the formula: —NR^(A) (in which R^(A) is a hydrogen atom, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: —ACONR_(B)R^(C) (in which R_(B) and R^(C) are the same or different and each a hydrogen atom or a lower alkyl group, or R^(B) and R^(C) may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group)), provided that when R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different and each a hydrogen atom, a lower alkyl group or a benzoyl group), a hydrogen atom, a hydroxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group, a lower alkoxy group, a lower alkanoyloxy-substituted lower alkyl group, a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (m and u are the same as defined above, R⁶ and R⁷ are the same or different and each a hydrogen atom or a lower alkyl group, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group), or an amino-substituted lower alkanoyloxy.group having optionally a lower alkyl substituent; or R² and R³ may bind together to form an oxo group or a lower alkylidene group; and when R is a group of the formula:

and R⁸ in said group is a hydrogen atom, a lower alkyl group, a hydroxy group, a halogen atom, a lower alkoxy group or an amino group, then R⁹ should not be a hydrogen atom, a phenyl-lower alkoxycarbonyl group, nor a group of the formula: —NR¹⁰R¹¹ (R¹¹ is a lower alkanoyl group or a phenoxy-lower alkanoyl group having optionally 1 to 3 substituents selected from a lower alkyl group and a lower alkoxy group on the phenyl ring), or when R¹ is a hydrogen atom, R² is a hydrogen atom, an amino group, a mono-lower alkylamino group or a di-lower alkylamino group, or R² and R³ may bind together to form an oxo group, then R⁹ should not be a phenyl group having optionally a substituent selected from a hydroxy group, a lower alkyl group, a lower alkoxy group and a lower alkanoyloxy group on the phenyl ring, or when R⁹ is a group of the formula:

 (n is 1 or 2), and G is a group of the formula:

 (R² and R³ are the same as defined above), then X should not be a methylene group nor a group of the formula: ═CH—, or when one of R¹⁰ and R¹¹ is a hydrogen atom, the other should not be a lower alkyl group, or a pharmaceutically acceptable salt thereof.
 63. A method for antagonizing oxytocin, which comprises administering to a warm-blooded animal including a human being a therapeutically effective amount of a benzoheterocyclic derivative of the following formula [1]:

wherein G is a group of the formula:

or a group of the formula:

R¹ is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group, an amino group having optionally a lower alkyl substituent, a carboxy-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, or an aminocarbonyl-lower alkoxy group having optionally a lower alkyl substituent, R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different, and each a hydrogen atom, a lower alkyl group having optionally a hydroxy substituent or a benzoyl group having optionally a halogen substituent on the phenyl ring); a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group; a lower alkanoyl group; or a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which m and u are each 0 or 1, but both m and u should not be simultaneously 0, A is a lower alkylene group, R⁶ and R⁷ are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, or R² and R³ may bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group, R is a pyridylcarbonyl group which may optionally have a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group; a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; a cycloalkylcarbonyl group; or a group of the formula:

 (in which p is 1 or 2, R⁸ is a hydrogen atom, a lower alkyl group, a hydroxy group, an amino group having optionally a lower alkanoyl substituent, a nitro group, a halogen atom or a lower alkoxy group, R⁹ is a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ is a hydrogen atom, a lower alkyl group, or a lower alkanoyl group having optionally a halogen substituent, R¹¹ is a lower alkyl group, a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the lower alkanoyl moiety, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a lower alkoxycarbonyl group having optionally a halogen substituent, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a phenoxy-lower alkoxycarbonyl group, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a phenyl-lower alkoxycarbonyl group, a group of the formula:

 a tetrahydroisoquinolylcarbonyl group, a benzoyl-lower alkyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a lower alkylsulfonyl group, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a phenyl-lower alkenylcarbonyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, or R¹⁰ and R¹¹ may bind together with the nitrogen atom to which they bond to form an isoindoline ring); a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a berizoyl group having optionally a lower alkyl substituent on the phenyl ring; a cycloalkyl group; a lower alkyl group; a lower alkylthio group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a saturated or unsaturated 5- to 11-membered heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: —(A)_(m)—CHR¹²R¹³ (in which A is the same as defined above, R¹² is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R¹³ is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1)), X is a methylene group, a single bond, a group of the formula: ═CH— or a group of the formula: —NR¹⁴— (in which R¹⁴ is a hydrogen atom, a lower alkyl group or a lower alkanoyl group), Y is a group of the formula: —NR^(A) (in which R^(A) is a hydrogen atom, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: —ACONR_(B)R^(C) (in which R_(B) and R^(C) are the same or different and each a hydrogen atom or a lower alkyl group, or R^(B) and R^(C) may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being-intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group)), provided that when R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different and each a hydrogen atom, a lower alkyl group or a benzoyl group), a hydrogen atom, a hydroxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group, a lower alkoxy group, a lower alkanoyloxy-substituted lower alkyl group, a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (m and u are the same as defined above, R⁶ and R⁷ are the same or different and each a hydrogen atom or a lower alkyl group, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group), or an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; or R² and R³ may bind together to form an oxo group or a lower alkylidene group; and when R is a group of the formula:

 and R⁸ in said group is a hydrogen atom, a lower alkyl group, a hydroxy group, a halogen atom, a lower alkoxy group or an amino group, then R⁹ should not be a hydrogen atom, a phenyl-lower alkoxycarbonyl group, nor a group of the formula: —NR¹⁰R¹¹ (R¹¹ is a lower alkanoyl group or a phenoxy-lower alkanoyl group having optionally 1 to 3 substituents selected from a lower alkyl group and a lower alkoxy group on the phenyl ring), or when R¹ is a hydrogen atom, R² is a hydrogen atom, an amino group, a mono-lower alkylamino group or a di-lower alkylamino group, or R² and R³ may bind together to form an oxo group, then R⁹ should not be a phenyl group having optionally a substituent selected from a hydroxy group, a lower alkyl group, a lower alkoxy group and a lower alkanoyloxy group on the phenyl ring, or when R⁹ is a group of the formula:

 (n is 1 or 2), and G is a group of the formula:

 (R² and R³ are the same as defined above), then X should not be a methylene group nor a group of the formula: ═CH—, or when one of R¹⁰ and R¹¹ is a hydrogen atom, the other should not be a lower alkyl group, or a pharmaceutically acceptable salt thereof.
 64. A method for agonizing vasopressin, which comprises administering to a warm-blooded animal including a human being a therapeutically effective amount of a benzoheterocyclic derivative of the following formula [1]:

wherein G is a group of the formula:

or a group of the formula:

R¹ is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group, an amino group having optionally a lower alkyl substituent, a carboxy-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, or an aminocarbonyl-lower alkoxy group having optionally a lower alkyl substituent, R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different, and each a hydrogen atom, a lower alkyl group having optionally a hydroxy substituent or a benzoyl group having optionally a halogen substituent on the phenyl ring); a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group; a lower alkanoyl group; or a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which m and u are each 0 or 1, but both m and u should not be simultaneously 0, A is a lower alkylene group, R⁶ and R⁷ are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, or R² and R³ may bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group, R is a pyridylcarbonyl group which may optionally have a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group; a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; a cycloalkylcarbonyl group; or a group of the formula:

 (in which p is 1 or 2, R⁸ is a hydrogen atom, a lower alkyl group, a hydroxy group, an amino group having optionally a lower alkanoyl substituent, a nitro group, a halogen atom or a lower alkoxy group, R⁹ is a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ is a hydrogen atom, a lower alkyl group, or a lower alkanoyl group having optionally a halogen substituent, R¹¹ is a lower alkyl group, a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the lower alkanoyl moiety, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a lower alkoxycarbonyl group having optionally a halogen substituent, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a phenoxy-lower alkoxycarbonyl group, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a phenyl-lower alkoxycarbonyl group, a group of the formula:

 a tetrahydroisoquinolylcarbonyl group, a benzoyl-lower alkyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a lower alkylsulfonyl group, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a phenyl-lower alkenylcarbonyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, or R¹⁰ and R¹¹ may bind together with the nitrogen atom to which they bond to form an isoindoline ring); a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a cycloalkyl group; a lower alkyl group; a lower alkylthio group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a saturated or unsaturated 5- to 11-membered heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: —(A)_(m)—CHR¹²R¹³ (in which A is the same as defined above, R¹² is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R¹³ is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1)), X is a methylene group, a single bond, a group of the formula: ═CH— or a group of the formula: —NR¹⁴— (in which R¹⁴ is a hydrogen atom, a lower alkyl group or a lower alkanoyl group), Y is a group of the formula: —NR^(A) (in which R^(A) is a hydrogen atom, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: —ACONR_(B)R^(C) (in which R_(B) and R^(C) are the same or different and each a hydrogen atom or a lower alkyl group, or R_(B) and R^(C) may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group)), or a pharmaceutically acceptable salt thereof.
 65. A process for preparing a benzoheterocyclic derivative of the following formula [1]:

wherein G is a group of the formula:

or a group of the formula:

R¹ is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group, an amino group having optionally a lower alkyl substituent, a carboxy-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, or an aminocarbonyl-lower alkoxy group having optionally a lower alkyl substituent, R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different, and each a hydrogen atom, a lower alkyl group having optionally a hydroxy substituent or a benzoyl group having optionally a halogen substituent on the phenyl ring); a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group; a lower alkanoyl group; or a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which m and u are each 0 or 1, but both m and u should not be simultaneously 0, A is a lower alkylene group, R⁶ and R⁷ are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group), R³ is a hydrogen atom or a hydroxy-substituted lower alkyl group, or R² and R³ may bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group, R is a pyridylcarbonyl group which may optionally have a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group; a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; a cycloalkylcarbonyl group; or a group of the formula:

 (in which p is 1 or 2, R⁸ is a hydrogen atom, a lower alkyl group, a hydroxy group, an amino group having optionally a lower alkanoyl substituent, a nitro group, a halogen atom or a lower alkoxy group, R⁹ is a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ is a hydrogen atom, a lower alkyl group, or a lower alkanoyl group having optionally a halogen substituent, R¹¹ is a lower alkyl group, a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the lower alkanoyl moiety, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a lower alkoxycarbonyl group having optionally a halogen substituent, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a phenoxy-lower alkoxycarbonyl group, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a phenyl-lower alkoxycarbonyl group, a group of the formula:

 a tetrahydroisoquinolylcarbonyl group, a benzoyl-lower alkyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a lower alkylsulfonyl group, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a phenyl-lower alkenylcarbonyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, or R¹⁰ and R¹¹ may bind together with the nitrogen atom to which they bond to form an isoindoline ring); a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a cycloalkyl group; a lower alkyl group; a lower alkylthio group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a saturated or unsaturated 5- to 11-membered heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: —(A)_(m)—CHR¹²R¹³ (in which A is the same as defined above, R¹² is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R¹³ is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1)), X is a methylene group, a single bond, a group of the formula: ═CH— or a group of the formula: —NR¹⁴— (in which R¹⁴ is a hydrogen atom, a lower alkyl group or a lower alkanoyl group), Y is a group of the formula: —NR^(A) (in which R^(A) is a hydrogen atom, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: -ACONR_(B)R^(C) (in which R_(B) and R^(C) are the same or different and each a hydrogen atom or a lower alkyl group, or R_(B) and R^(C) may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group)), provided that when R² is a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different and each a hydrogen atom, a lower alkyl group or a benzoyl group), a hydrogen atom, a hydroxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group, a lower alkoxy group, a lower alkanoyloxy-substituted lower alkyl group, a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (m and u are the same as defined above, R⁶ and R⁷ are the same or different and each a hydrogen atom or a lower alkyl group, or R⁶ and R⁷ may bind together with the nitrogen atom to which they bond to form a 5- to 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group), or an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; or R² and R³ may bind together to form an oxo group or a lower alkylidene group; and when R is a group of the formula:

 and R⁸ in said group is a hydrogen atom, a lower alkyl group, a hydroxy group, a halogen atom, a lower alkoxy group or an amino group, then R⁹ should not be a hydrogen atom, a phenyl-lower alkoxycarbonyl group, nor a group of the formula: —NR¹⁰R¹¹ (R¹¹ is a lower alkanoyl group or a phenoxy-lower alkanoyl group having optionally 1 to 3 substituents selected from a lower alkyl group and a lower alkoxy group on the phenyl ring), or when R¹ is a hydrogen atom, R² is a hydrogen atom, an amino group, a mono-lower alkylamino group or a di-lower alkylamino group, or R² and R³ may bind together to form an oxo group, then R⁹ should not be a phenyl group having optionally a substituent selected from a hydroxy group, a lower alkyl group, a lower alkoxy group and a lower alkanoyloxy group on the phenyl ring, or when R⁹ is a group of the formula:

 (n is 1 or 2), and G is a group of the formula:

 (R² and R³ are the same as defined above), then X should not be a methylene group nor a group of the formula: ═CH—, or when one of R¹⁰ and R¹¹ is a hydrogen atom, the other should not be a lower alkyl group, or when R¹ and R² are simultaneously a hydrogen atom, then R should not be unsubstituted pyridylcarbonyl group, unsubstituted thienylcarbonyl group, unsubstituted thiazolylcarbonyl group, nor a cycloalkylcarbonyl group, or when R³ is a hydrogen atom, R² is a hydrogen atom, an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent, a lower alkoxycarbonyl-substituted lower alkoxy group, a hydroxy group, a lower alkoxy group, a group of the formula: —(O)_(m)—A—(CO)_(u)NR⁶R⁷ (in which R⁶ and R⁷ are the same or different and each a hydrogen atom or a lower alkyl group, m is 1, u is 0 or 1) or a group of the formula: —NR⁴R⁵ (in which R⁴ and R⁵ are the same or different and each a hydrogen atom or a lower alkyl group), or R² and R³ may bind together to form an oxo group or a lower alkylidene group, then R⁹ should not be a group of the formula: —NR¹⁰R¹¹ (in which R¹⁰ is a lower alkyl group, R¹¹ is a lower alkyl group), a hydrogen atom, a lower alkylthio group, a lower alkoxy group nor a lower alkyl group, which comprises reacting a benzoheterocyclic compound of the formula [2]:

 wherein R¹ and G are the same as defined above, with a carboxylic acid compound of the formula [3]:

 wherein R is the same as defined above, by a conventional amido bond producing reaction. 